Conference Coverage

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

In recent years, innovative use of bispecific antibodies and CAR T-cell therapy has ushered in an era when many patients with relapsed/refractory acute lymphoblastic leukemia (ALL) — who once had prognoses of 6 months or less — now survive for multiple years with the malignancy, and some are cured.

The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.

“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.

MD Anderson Cancer Center

His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.

“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.

This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.

Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.

Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.

Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.

Memorial Sloan Kettering Cancer Center

In recent years, innovative use of bispecific antibodies and CAR T-cell therapy has ushered in an era when many patients with relapsed/refractory acute lymphoblastic leukemia (ALL) — who once had prognoses of 6 months or less — now survive for multiple years with the malignancy, and some are cured.

The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.

“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.

MD Anderson Cancer Center

His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.

“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.

This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.

Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.

Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.

Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.

Memorial Sloan Kettering Cancer Center

In recent years, innovative use of bispecific antibodies and CAR T-cell therapy has ushered in an era when many patients with relapsed/refractory acute lymphoblastic leukemia (ALL) — who once had prognoses of 6 months or less — now survive for multiple years with the malignancy, and some are cured.

The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.

“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.

MD Anderson Cancer Center

His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.

“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.

This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.

Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.

Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.

Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.

Memorial Sloan Kettering Cancer Center

SAN DIEGO — The number of solid organ transplant survivors is on the rise, a dermatologist told colleagues, and they face unique challenges from higher risks for skin cancer and skin infections because of their suppressed immune systems.

“There are over 450,000 people with a solid organ transplant living in the United States. If you do the math, that works out to about 40 organ transplant recipients for every dermatologist, so there’s a lot of them out there for us to take care of,” Sean Christensen, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, said at the annual meeting of the American Academy of Dermatology (AAD). “If we expand that umbrella to include all types of immunosuppression, that’s over 4 million adults in the US.”

Dr. Christensen encouraged dermatologists to be aware of the varying risks for immunosuppressive drugs and best screening practices for these patients, and to take advantage of a validated skin cancer risk assessment tool for transplant patients.

During his presentation, he highlighted five classes of immunosuppressive drugs and their associated skin cancer risks:

• Calcineurin inhibitors (tacrolimus or cyclosporine), which cause severe immune suppression and pose a severe skin cancer risk. They may also cause gingival hyperplasia and sebaceous hyperplasia.
• Antimetabolites (mycophenolate mofetil or azathioprine), which cause moderate to severe immune suppression and pose a severe skin cancer risk.
• Mammalian target of rapamycin inhibitors (sirolimus or everolimus), which cause severe immune suppression and pose a moderate skin cancer risk. They also impair wound healing.
• Corticosteroids (prednisone), which cause mild to severe immune suppression and pose a minimal skin cancer risk.
• A decoy receptor protein (belatacept), which causes severe immune suppression and poses a mild skin cancer risk.

“Most of our solid-organ transplant recipients will be on both a calcineurin inhibitor and an antimetabolite,” Dr. Christensen said. “In addition to the skin cancer risk associated with immunosuppression, there is an additive risk” that is a direct effect of these medications on the skin. “That means our transplant recipients have a severely and disproportionate increase in skin cancer,” he noted.

Up to half of solid-organ transplant recipients will develop skin cancer, Dr. Christensen said. These patients have a sixfold to 10-fold increased risk for basal cell carcinoma (BCC), a 35- to 65-fold increased risk for squamous cell carcinoma (SCC), a twofold to sevenfold increased risk for melanoma, and a 16- to 100-fold increased risk for Merkel cell carcinoma.

Transplant recipients with SCC, he said, have a twofold to threefold higher risk for metastasis (4%-8% nodal metastasis) and twofold to fivefold higher risk for death (2%-7% mortality) from SCC.

As for other kinds of immunosuppression, HIV positivity, treatment with 6-mercaptopurine or azathioprine (for inflammatory bowel disease and rheumatoid arthritis), and antitumor necrosis factor agents (for psoriasis, inflammatory bowel disease, and rheumatoid arthritis) have been linked in studies to a higher risk for nonmelanoma skin cancer.

Dr. Christensen also highlighted graft-versus-host disease (GVHD). “It does look like there is a disproportionate and increased risk of SCC of the oropharynx and of the skin in patients who have chronic GVHD. This is probably due to a combination of both the immunosuppressive medications that are required but also from chronic and ongoing inflammation in the skin.”

Chronic GVHD has been linked to a 5.3-fold increase in the risk for SCC and a twofold increase in the risk for BCC, he added.

Moreover, new medications for treating GVHD have been linked to an increased risk for SCC, including a 3.2-fold increased risk for SCC associated with ruxolitinib, a Janus kinase (JAK) 1 and JAK2 inhibitor, in a study of patients with polycythemia vera and myelofibrosis; and a case report of SCC in a patient treated with belumosudil, a rho-associated coiled-coil-containing protein kinase-2 kinase inhibitor, for chronic GVHD. Risk for SCC appears to increase based on duration of use with voriconazole, an antifungal, which, he said, is a potent photosynthesizer.

Dr. Christensen also noted the higher risk for infections in immunocompromised patients and added that these patients can develop inflammatory disease despite immunosuppression:

Staphylococcus, Streptococcus, and Dermatophytes are the most common skin pathogens in these patients. There’s a significantly increased risk for reactivation of herpes simplex, varicella-zoster viruses, and cytomegalovirus. Opportunistic and disseminated fungal infections, such as mycobacteria, Candida, histoplasma, cryptococcus, aspergillus, and mucormycosis, can also appear.

More than 80% of transplant recipients develop molluscum and verruca vulgaris/human papillomavirus infection. They may also develop noninfectious inflammatory dermatoses.

Risk Calculator

What can dermatologists do to help transplant patients? Dr. Christensen highlighted the Skin and UV Neoplasia Transplant Risk Assessment Calculator, which predicts skin cancer risk based on points given for race, gender, skin cancer history, age at transplant, and site of transplant.

The tool, validated in a 2023 study of transplant recipients in Europe, is available online and as an app. It makes recommendations to users about when patients should have initial skin screening exams. Those with the most risk — 45% at 5 years — should be screened within 6 months. “We can use [the tool] to triage these cases when we first meet them and get them plugged into the appropriate care,” Dr. Christensen said.

He recommended seeing high-risk patients at least annually. Patients with a prior SCC and a heavy burden of actinic keratosis should be followed more frequently, he said.

In regard to SCC, he highlighted a 2024 study of solid organ transplant recipients that found the risk for a second SCC after a first SCC was 74%, the risk for a third SCC after a second SCC was 83%, and the risk for another SCC after five SCCs was 92%.

Dr. Christensen disclosed relationships with Canfield Scientific Inc. (consulting), Inhibitor Therapeutics (advisory board), and Sol-Gel Technologies Ltd. (grants/research funding).

A version of this article first appeared on Medscape.com.

SAN DIEGO — The number of solid organ transplant survivors is on the rise, a dermatologist told colleagues, and they face unique challenges from higher risks for skin cancer and skin infections because of their suppressed immune systems.

“There are over 450,000 people with a solid organ transplant living in the United States. If you do the math, that works out to about 40 organ transplant recipients for every dermatologist, so there’s a lot of them out there for us to take care of,” Sean Christensen, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, said at the annual meeting of the American Academy of Dermatology (AAD). “If we expand that umbrella to include all types of immunosuppression, that’s over 4 million adults in the US.”

Dr. Christensen encouraged dermatologists to be aware of the varying risks for immunosuppressive drugs and best screening practices for these patients, and to take advantage of a validated skin cancer risk assessment tool for transplant patients.

During his presentation, he highlighted five classes of immunosuppressive drugs and their associated skin cancer risks:

• Calcineurin inhibitors (tacrolimus or cyclosporine), which cause severe immune suppression and pose a severe skin cancer risk. They may also cause gingival hyperplasia and sebaceous hyperplasia.
• Antimetabolites (mycophenolate mofetil or azathioprine), which cause moderate to severe immune suppression and pose a severe skin cancer risk.
• Mammalian target of rapamycin inhibitors (sirolimus or everolimus), which cause severe immune suppression and pose a moderate skin cancer risk. They also impair wound healing.
• Corticosteroids (prednisone), which cause mild to severe immune suppression and pose a minimal skin cancer risk.
• A decoy receptor protein (belatacept), which causes severe immune suppression and poses a mild skin cancer risk.

“Most of our solid-organ transplant recipients will be on both a calcineurin inhibitor and an antimetabolite,” Dr. Christensen said. “In addition to the skin cancer risk associated with immunosuppression, there is an additive risk” that is a direct effect of these medications on the skin. “That means our transplant recipients have a severely and disproportionate increase in skin cancer,” he noted.

Up to half of solid-organ transplant recipients will develop skin cancer, Dr. Christensen said. These patients have a sixfold to 10-fold increased risk for basal cell carcinoma (BCC), a 35- to 65-fold increased risk for squamous cell carcinoma (SCC), a twofold to sevenfold increased risk for melanoma, and a 16- to 100-fold increased risk for Merkel cell carcinoma.

Transplant recipients with SCC, he said, have a twofold to threefold higher risk for metastasis (4%-8% nodal metastasis) and twofold to fivefold higher risk for death (2%-7% mortality) from SCC.

As for other kinds of immunosuppression, HIV positivity, treatment with 6-mercaptopurine or azathioprine (for inflammatory bowel disease and rheumatoid arthritis), and antitumor necrosis factor agents (for psoriasis, inflammatory bowel disease, and rheumatoid arthritis) have been linked in studies to a higher risk for nonmelanoma skin cancer.

Dr. Christensen also highlighted graft-versus-host disease (GVHD). “It does look like there is a disproportionate and increased risk of SCC of the oropharynx and of the skin in patients who have chronic GVHD. This is probably due to a combination of both the immunosuppressive medications that are required but also from chronic and ongoing inflammation in the skin.”

Chronic GVHD has been linked to a 5.3-fold increase in the risk for SCC and a twofold increase in the risk for BCC, he added.

Moreover, new medications for treating GVHD have been linked to an increased risk for SCC, including a 3.2-fold increased risk for SCC associated with ruxolitinib, a Janus kinase (JAK) 1 and JAK2 inhibitor, in a study of patients with polycythemia vera and myelofibrosis; and a case report of SCC in a patient treated with belumosudil, a rho-associated coiled-coil-containing protein kinase-2 kinase inhibitor, for chronic GVHD. Risk for SCC appears to increase based on duration of use with voriconazole, an antifungal, which, he said, is a potent photosynthesizer.

Dr. Christensen also noted the higher risk for infections in immunocompromised patients and added that these patients can develop inflammatory disease despite immunosuppression:

Staphylococcus, Streptococcus, and Dermatophytes are the most common skin pathogens in these patients. There’s a significantly increased risk for reactivation of herpes simplex, varicella-zoster viruses, and cytomegalovirus. Opportunistic and disseminated fungal infections, such as mycobacteria, Candida, histoplasma, cryptococcus, aspergillus, and mucormycosis, can also appear.

More than 80% of transplant recipients develop molluscum and verruca vulgaris/human papillomavirus infection. They may also develop noninfectious inflammatory dermatoses.

Risk Calculator

What can dermatologists do to help transplant patients? Dr. Christensen highlighted the Skin and UV Neoplasia Transplant Risk Assessment Calculator, which predicts skin cancer risk based on points given for race, gender, skin cancer history, age at transplant, and site of transplant.

The tool, validated in a 2023 study of transplant recipients in Europe, is available online and as an app. It makes recommendations to users about when patients should have initial skin screening exams. Those with the most risk — 45% at 5 years — should be screened within 6 months. “We can use [the tool] to triage these cases when we first meet them and get them plugged into the appropriate care,” Dr. Christensen said.

He recommended seeing high-risk patients at least annually. Patients with a prior SCC and a heavy burden of actinic keratosis should be followed more frequently, he said.

In regard to SCC, he highlighted a 2024 study of solid organ transplant recipients that found the risk for a second SCC after a first SCC was 74%, the risk for a third SCC after a second SCC was 83%, and the risk for another SCC after five SCCs was 92%.

Dr. Christensen disclosed relationships with Canfield Scientific Inc. (consulting), Inhibitor Therapeutics (advisory board), and Sol-Gel Technologies Ltd. (grants/research funding).

A version of this article first appeared on Medscape.com.

SAN DIEGO — The number of solid organ transplant survivors is on the rise, a dermatologist told colleagues, and they face unique challenges from higher risks for skin cancer and skin infections because of their suppressed immune systems.

“There are over 450,000 people with a solid organ transplant living in the United States. If you do the math, that works out to about 40 organ transplant recipients for every dermatologist, so there’s a lot of them out there for us to take care of,” Sean Christensen, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, said at the annual meeting of the American Academy of Dermatology (AAD). “If we expand that umbrella to include all types of immunosuppression, that’s over 4 million adults in the US.”

Dr. Christensen encouraged dermatologists to be aware of the varying risks for immunosuppressive drugs and best screening practices for these patients, and to take advantage of a validated skin cancer risk assessment tool for transplant patients.

During his presentation, he highlighted five classes of immunosuppressive drugs and their associated skin cancer risks:

• Calcineurin inhibitors (tacrolimus or cyclosporine), which cause severe immune suppression and pose a severe skin cancer risk. They may also cause gingival hyperplasia and sebaceous hyperplasia.
• Antimetabolites (mycophenolate mofetil or azathioprine), which cause moderate to severe immune suppression and pose a severe skin cancer risk.
• Mammalian target of rapamycin inhibitors (sirolimus or everolimus), which cause severe immune suppression and pose a moderate skin cancer risk. They also impair wound healing.
• Corticosteroids (prednisone), which cause mild to severe immune suppression and pose a minimal skin cancer risk.
• A decoy receptor protein (belatacept), which causes severe immune suppression and poses a mild skin cancer risk.

“Most of our solid-organ transplant recipients will be on both a calcineurin inhibitor and an antimetabolite,” Dr. Christensen said. “In addition to the skin cancer risk associated with immunosuppression, there is an additive risk” that is a direct effect of these medications on the skin. “That means our transplant recipients have a severely and disproportionate increase in skin cancer,” he noted.

Up to half of solid-organ transplant recipients will develop skin cancer, Dr. Christensen said. These patients have a sixfold to 10-fold increased risk for basal cell carcinoma (BCC), a 35- to 65-fold increased risk for squamous cell carcinoma (SCC), a twofold to sevenfold increased risk for melanoma, and a 16- to 100-fold increased risk for Merkel cell carcinoma.

Transplant recipients with SCC, he said, have a twofold to threefold higher risk for metastasis (4%-8% nodal metastasis) and twofold to fivefold higher risk for death (2%-7% mortality) from SCC.

As for other kinds of immunosuppression, HIV positivity, treatment with 6-mercaptopurine or azathioprine (for inflammatory bowel disease and rheumatoid arthritis), and antitumor necrosis factor agents (for psoriasis, inflammatory bowel disease, and rheumatoid arthritis) have been linked in studies to a higher risk for nonmelanoma skin cancer.

Dr. Christensen also highlighted graft-versus-host disease (GVHD). “It does look like there is a disproportionate and increased risk of SCC of the oropharynx and of the skin in patients who have chronic GVHD. This is probably due to a combination of both the immunosuppressive medications that are required but also from chronic and ongoing inflammation in the skin.”

Chronic GVHD has been linked to a 5.3-fold increase in the risk for SCC and a twofold increase in the risk for BCC, he added.

Moreover, new medications for treating GVHD have been linked to an increased risk for SCC, including a 3.2-fold increased risk for SCC associated with ruxolitinib, a Janus kinase (JAK) 1 and JAK2 inhibitor, in a study of patients with polycythemia vera and myelofibrosis; and a case report of SCC in a patient treated with belumosudil, a rho-associated coiled-coil-containing protein kinase-2 kinase inhibitor, for chronic GVHD. Risk for SCC appears to increase based on duration of use with voriconazole, an antifungal, which, he said, is a potent photosynthesizer.

Dr. Christensen also noted the higher risk for infections in immunocompromised patients and added that these patients can develop inflammatory disease despite immunosuppression:

Staphylococcus, Streptococcus, and Dermatophytes are the most common skin pathogens in these patients. There’s a significantly increased risk for reactivation of herpes simplex, varicella-zoster viruses, and cytomegalovirus. Opportunistic and disseminated fungal infections, such as mycobacteria, Candida, histoplasma, cryptococcus, aspergillus, and mucormycosis, can also appear.

More than 80% of transplant recipients develop molluscum and verruca vulgaris/human papillomavirus infection. They may also develop noninfectious inflammatory dermatoses.

Risk Calculator

What can dermatologists do to help transplant patients? Dr. Christensen highlighted the Skin and UV Neoplasia Transplant Risk Assessment Calculator, which predicts skin cancer risk based on points given for race, gender, skin cancer history, age at transplant, and site of transplant.

The tool, validated in a 2023 study of transplant recipients in Europe, is available online and as an app. It makes recommendations to users about when patients should have initial skin screening exams. Those with the most risk — 45% at 5 years — should be screened within 6 months. “We can use [the tool] to triage these cases when we first meet them and get them plugged into the appropriate care,” Dr. Christensen said.

He recommended seeing high-risk patients at least annually. Patients with a prior SCC and a heavy burden of actinic keratosis should be followed more frequently, he said.

In regard to SCC, he highlighted a 2024 study of solid organ transplant recipients that found the risk for a second SCC after a first SCC was 74%, the risk for a third SCC after a second SCC was 83%, and the risk for another SCC after five SCCs was 92%.

Dr. Christensen disclosed relationships with Canfield Scientific Inc. (consulting), Inhibitor Therapeutics (advisory board), and Sol-Gel Technologies Ltd. (grants/research funding).

A version of this article first appeared on Medscape.com.

SAN DIEGO — In patients with alopecia areata (AA), the decision of when to give up on JAK inhibitors because of an inadequate response is being complicated by long-term follow-up showing that some patients accrue hair very slowly, according to late breaker data presented at the annual meeting of the American Academy of Dermatology.

Although the majority respond within months, response curves have so far climbed for as long as patients are followed, allowing many with disappointing early results to catch up, according to Rodney D. Sinclair, MD, professor of dermatology at the University of Melbourne, Australia.

His remarks were derived specifically from new long-term follow-up with baricitinib, the first JAK inhibitor approved for AA, but the pattern appears to be similar with ritlecitinib, the only other JAK inhibitor approved for AA, and for several if not all JAK inhibitors in phase 3 AA trials.

“We have had patients on baricitinib where not much was happening at 18 months, but now, at 4 years, they have a SALT score of zero,” Dr. Sinclair reported

A Severity of Alopecia Tool (SALT) score of 0 signifies complete hair regrowth. On a scale with a maximum score of 100 (complete hair loss), a SALT score of 20 or less, signaling clinical success, has been a primary endpoint in many JAK inhibitor trials, including those conducted with baricitinib.

Providing the most recent analysis in patients with severe AA participating in the phase 3 BRAVE-AA1 and BRAVE-AA2 trials of baricitinib, which were published together in 2022, Dr. Sinclair broke the data down into responders, mixed responders, and nonresponders at 52 weeks. The proportion of patients who responded with even longer follow-up were then tallied.

In the as-observed responses over time, the trajectory of response continued to climb through 76 weeks of follow-up in all three groups.

Relative to the 44.5% rate of overall response (SALT ≤ 20 ) at 52 weeks, there was some further growth in every group maintained on JAK inhibitor therapy over longer follow-up. In Dr. Sinclair’s late breaking analysis, this did not include nonresponders, who stopped therapy by week 52, but 78.4% of the combined responders and mixed responders who remained on treatment had reached treatment success at 76 weeks.
 

Response Curves Climb More Slowly With Severe Alopecia

While improvement in SALT scores was even seen in nonresponders over time as long as they remained on therapy, Dr. Sinclair reported that response curves tended to climb more slowly in those with more severe alopecia at baseline. Yet, they still climbed. For example, 28.1% of those with a baseline SALT score of 95 to 100 had reached treatment success at week 52, but the proportion had climbed to 35.4% by week 76.

The response curves climbed more quickly among those with a SALT score between 50 and 95 at baseline than among those with more severe alopecia, but the differences in SALT scores at 52 weeks and 76 weeks among patients in this range of baseline SALT scores were small.

Basically, “those with a SALT score of 94 did just as well as those with a SALT score of 51 when followed long-term,” he said, noting that this was among several findings that confounded expectations.

Duration of AA was found to be an important prognostic factor, with 4 years emerging as a general threshold separating those with a diminished likelihood of benefit relative to those with a shorter AA duration.

“When the duration of AA is more than 4 years, the response to any JAK inhibitor seems to fall off a cliff,” Dr. Sinclair said.

To clarify this observation, Dr. Sinclair made an analogy between acute and chronic urticaria. Chronicity appears to change the pathophysiology of both urticaria and AA, making durable remissions more difficult to achieve if the inflammatory response was persistently upregulated, he said.

The delayed responses in some patients “suggests that it is not enough to control inflammation for the hair to regrow. You actually have to activate the hair to grow as well as treat the inflammation,” Dr. Sinclair said.

This heterogeneity that has been observed in the speed of AA response to JAK inhibitors might be explained at least in part by the individual differences in hair growth activation. For ritlecitinib, the only other JAK inhibitor approved for AA to date, 62% were categorized as responders in the registration ALLEGRO trials, but only 44% were early responders, meaning SALT scores of ≤ 20 by week 24, according to a summary published last year. Of the remaining 16%, 11% were middle responders, meaning a SALT score of ≤ 20 reached at week 48, and 6% were late responders, meaning a SALT score of ≤ 20 reached at week 96.

In the context of late breaking 68-week data with deuruxolitinib, an oral JAK inhibitor currently under FDA review for treating moderate to severe AA, presented in the same AAD session as Dr. Sinclair’s baricitinib data, Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, described similar long-term response curves. At 24 weeks, the SALT ≤ 20 response was achieved in 34.9% of patients, but climbed to 62.8% with continuous therapy over 68 weeks.

Time Factor Is Important for Response

“What we are learning is that patients keep getting better over time,” Dr. Sinclair said. Asked specifically how long he would treat a patient before giving up, he acknowledged that he used to consider 6 months adequate, but that he has now changed his mind.

“It might be that even 2 years is too short,” he said, although he conceded that a trial of therapy for this long “might be an issue for third-part payers.”

Asked to comment, Melissa Piliang, MD, chair of the department of dermatology at the Cleveland Clinic, agreed with the principle that early responses are not necessarily predictive of complete response.

Dr. Piliang

SAN DIEGO — In patients with alopecia areata (AA), the decision of when to give up on JAK inhibitors because of an inadequate response is being complicated by long-term follow-up showing that some patients accrue hair very slowly, according to late breaker data presented at the annual meeting of the American Academy of Dermatology.

Although the majority respond within months, response curves have so far climbed for as long as patients are followed, allowing many with disappointing early results to catch up, according to Rodney D. Sinclair, MD, professor of dermatology at the University of Melbourne, Australia.

His remarks were derived specifically from new long-term follow-up with baricitinib, the first JAK inhibitor approved for AA, but the pattern appears to be similar with ritlecitinib, the only other JAK inhibitor approved for AA, and for several if not all JAK inhibitors in phase 3 AA trials.

“We have had patients on baricitinib where not much was happening at 18 months, but now, at 4 years, they have a SALT score of zero,” Dr. Sinclair reported

A Severity of Alopecia Tool (SALT) score of 0 signifies complete hair regrowth. On a scale with a maximum score of 100 (complete hair loss), a SALT score of 20 or less, signaling clinical success, has been a primary endpoint in many JAK inhibitor trials, including those conducted with baricitinib.

Providing the most recent analysis in patients with severe AA participating in the phase 3 BRAVE-AA1 and BRAVE-AA2 trials of baricitinib, which were published together in 2022, Dr. Sinclair broke the data down into responders, mixed responders, and nonresponders at 52 weeks. The proportion of patients who responded with even longer follow-up were then tallied.

In the as-observed responses over time, the trajectory of response continued to climb through 76 weeks of follow-up in all three groups.

Relative to the 44.5% rate of overall response (SALT ≤ 20 ) at 52 weeks, there was some further growth in every group maintained on JAK inhibitor therapy over longer follow-up. In Dr. Sinclair’s late breaking analysis, this did not include nonresponders, who stopped therapy by week 52, but 78.4% of the combined responders and mixed responders who remained on treatment had reached treatment success at 76 weeks.
 

Response Curves Climb More Slowly With Severe Alopecia

While improvement in SALT scores was even seen in nonresponders over time as long as they remained on therapy, Dr. Sinclair reported that response curves tended to climb more slowly in those with more severe alopecia at baseline. Yet, they still climbed. For example, 28.1% of those with a baseline SALT score of 95 to 100 had reached treatment success at week 52, but the proportion had climbed to 35.4% by week 76.

The response curves climbed more quickly among those with a SALT score between 50 and 95 at baseline than among those with more severe alopecia, but the differences in SALT scores at 52 weeks and 76 weeks among patients in this range of baseline SALT scores were small.

Basically, “those with a SALT score of 94 did just as well as those with a SALT score of 51 when followed long-term,” he said, noting that this was among several findings that confounded expectations.

Duration of AA was found to be an important prognostic factor, with 4 years emerging as a general threshold separating those with a diminished likelihood of benefit relative to those with a shorter AA duration.

“When the duration of AA is more than 4 years, the response to any JAK inhibitor seems to fall off a cliff,” Dr. Sinclair said.

To clarify this observation, Dr. Sinclair made an analogy between acute and chronic urticaria. Chronicity appears to change the pathophysiology of both urticaria and AA, making durable remissions more difficult to achieve if the inflammatory response was persistently upregulated, he said.

The delayed responses in some patients “suggests that it is not enough to control inflammation for the hair to regrow. You actually have to activate the hair to grow as well as treat the inflammation,” Dr. Sinclair said.

This heterogeneity that has been observed in the speed of AA response to JAK inhibitors might be explained at least in part by the individual differences in hair growth activation. For ritlecitinib, the only other JAK inhibitor approved for AA to date, 62% were categorized as responders in the registration ALLEGRO trials, but only 44% were early responders, meaning SALT scores of ≤ 20 by week 24, according to a summary published last year. Of the remaining 16%, 11% were middle responders, meaning a SALT score of ≤ 20 reached at week 48, and 6% were late responders, meaning a SALT score of ≤ 20 reached at week 96.

In the context of late breaking 68-week data with deuruxolitinib, an oral JAK inhibitor currently under FDA review for treating moderate to severe AA, presented in the same AAD session as Dr. Sinclair’s baricitinib data, Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, described similar long-term response curves. At 24 weeks, the SALT ≤ 20 response was achieved in 34.9% of patients, but climbed to 62.8% with continuous therapy over 68 weeks.

Time Factor Is Important for Response

“What we are learning is that patients keep getting better over time,” Dr. Sinclair said. Asked specifically how long he would treat a patient before giving up, he acknowledged that he used to consider 6 months adequate, but that he has now changed his mind.

“It might be that even 2 years is too short,” he said, although he conceded that a trial of therapy for this long “might be an issue for third-part payers.”

Asked to comment, Melissa Piliang, MD, chair of the department of dermatology at the Cleveland Clinic, agreed with the principle that early responses are not necessarily predictive of complete response.

Dr. Piliang

SAN DIEGO — In patients with alopecia areata (AA), the decision of when to give up on JAK inhibitors because of an inadequate response is being complicated by long-term follow-up showing that some patients accrue hair very slowly, according to late breaker data presented at the annual meeting of the American Academy of Dermatology.

Although the majority respond within months, response curves have so far climbed for as long as patients are followed, allowing many with disappointing early results to catch up, according to Rodney D. Sinclair, MD, professor of dermatology at the University of Melbourne, Australia.

His remarks were derived specifically from new long-term follow-up with baricitinib, the first JAK inhibitor approved for AA, but the pattern appears to be similar with ritlecitinib, the only other JAK inhibitor approved for AA, and for several if not all JAK inhibitors in phase 3 AA trials.

“We have had patients on baricitinib where not much was happening at 18 months, but now, at 4 years, they have a SALT score of zero,” Dr. Sinclair reported

A Severity of Alopecia Tool (SALT) score of 0 signifies complete hair regrowth. On a scale with a maximum score of 100 (complete hair loss), a SALT score of 20 or less, signaling clinical success, has been a primary endpoint in many JAK inhibitor trials, including those conducted with baricitinib.

Providing the most recent analysis in patients with severe AA participating in the phase 3 BRAVE-AA1 and BRAVE-AA2 trials of baricitinib, which were published together in 2022, Dr. Sinclair broke the data down into responders, mixed responders, and nonresponders at 52 weeks. The proportion of patients who responded with even longer follow-up were then tallied.

In the as-observed responses over time, the trajectory of response continued to climb through 76 weeks of follow-up in all three groups.

Relative to the 44.5% rate of overall response (SALT ≤ 20 ) at 52 weeks, there was some further growth in every group maintained on JAK inhibitor therapy over longer follow-up. In Dr. Sinclair’s late breaking analysis, this did not include nonresponders, who stopped therapy by week 52, but 78.4% of the combined responders and mixed responders who remained on treatment had reached treatment success at 76 weeks.
 

Response Curves Climb More Slowly With Severe Alopecia

While improvement in SALT scores was even seen in nonresponders over time as long as they remained on therapy, Dr. Sinclair reported that response curves tended to climb more slowly in those with more severe alopecia at baseline. Yet, they still climbed. For example, 28.1% of those with a baseline SALT score of 95 to 100 had reached treatment success at week 52, but the proportion had climbed to 35.4% by week 76.

The response curves climbed more quickly among those with a SALT score between 50 and 95 at baseline than among those with more severe alopecia, but the differences in SALT scores at 52 weeks and 76 weeks among patients in this range of baseline SALT scores were small.

Basically, “those with a SALT score of 94 did just as well as those with a SALT score of 51 when followed long-term,” he said, noting that this was among several findings that confounded expectations.

Duration of AA was found to be an important prognostic factor, with 4 years emerging as a general threshold separating those with a diminished likelihood of benefit relative to those with a shorter AA duration.

“When the duration of AA is more than 4 years, the response to any JAK inhibitor seems to fall off a cliff,” Dr. Sinclair said.

To clarify this observation, Dr. Sinclair made an analogy between acute and chronic urticaria. Chronicity appears to change the pathophysiology of both urticaria and AA, making durable remissions more difficult to achieve if the inflammatory response was persistently upregulated, he said.

The delayed responses in some patients “suggests that it is not enough to control inflammation for the hair to regrow. You actually have to activate the hair to grow as well as treat the inflammation,” Dr. Sinclair said.

This heterogeneity that has been observed in the speed of AA response to JAK inhibitors might be explained at least in part by the individual differences in hair growth activation. For ritlecitinib, the only other JAK inhibitor approved for AA to date, 62% were categorized as responders in the registration ALLEGRO trials, but only 44% were early responders, meaning SALT scores of ≤ 20 by week 24, according to a summary published last year. Of the remaining 16%, 11% were middle responders, meaning a SALT score of ≤ 20 reached at week 48, and 6% were late responders, meaning a SALT score of ≤ 20 reached at week 96.

In the context of late breaking 68-week data with deuruxolitinib, an oral JAK inhibitor currently under FDA review for treating moderate to severe AA, presented in the same AAD session as Dr. Sinclair’s baricitinib data, Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, described similar long-term response curves. At 24 weeks, the SALT ≤ 20 response was achieved in 34.9% of patients, but climbed to 62.8% with continuous therapy over 68 weeks.

Time Factor Is Important for Response

“What we are learning is that patients keep getting better over time,” Dr. Sinclair said. Asked specifically how long he would treat a patient before giving up, he acknowledged that he used to consider 6 months adequate, but that he has now changed his mind.

“It might be that even 2 years is too short,” he said, although he conceded that a trial of therapy for this long “might be an issue for third-part payers.”

Asked to comment, Melissa Piliang, MD, chair of the department of dermatology at the Cleveland Clinic, agreed with the principle that early responses are not necessarily predictive of complete response.

Dr. Piliang

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Patients with mild hidradenitis suppurativa (HS) treated with ruxolitinib cream experienced a greater reduction in the abscess and inflammatory nodule (AN) count from baseline to week 16 than those who applied a vehicle cream, in a phase 2 trial.

“HS is a chronic, recurring inflammatory skin disease that is associated with painful inflammatory modules and abscesses,” said presenting author Martina J. Porter, MD, a dermatologist at Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts. Dr. Porter presented the data during a late-breaking session at the annual meeting of the American Academy of Dermatology.

“Over time, these patients may progress to having tunnels, ulcerations, malodorous discharge, and permanent scarring,” she said. “Currently, there are no approved therapies for milder HS, and the standard treatments that we apply in clinical practice are often inadequate.”

Ruxolitinib is a selective Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated efficacy in other inflammatory and autoimmune skin diseases. Ruxolitinib cream, 1.5%, is approved for treating mild to moderate atopic dermatitis and nonsegmental vitiligo in patients ages 12 years and older.

The phase 2 double-blind, vehicle-controlled trial evaluated the efficacy and safety of ruxolitinib cream for mild HS. Researchers assigned 69 adults with Hurley stage I or II HS to receive 1.5% ruxolitinib cream or vehicle cream twice daily for 16 weeks. The primary endpoint was the change from baseline in AN count at week 16. To be eligible, patients had to have an AN count between 3 and 10.

“This is much more mild than what we have seen in any systemic therapy trials,” Dr. Porter said. “And, if patients had 3 lesions, they all needed to be in one anatomic area, but if they had 4-10 lesions, they had to have two anatomic areas involved. Also, no patients with active draining tunnels were allowed in the study.”

Of the 69 patients, 34 received ruxolitinib cream and 35 received vehicle. About 51% of patients in the vehicle arm were Black and 34% were White, while about 32% of patients in the ruxolitinib arm were Black and 56% were White.

The mean age of patients overall was 29 years, and about half the patients in both study arms had Hurley stage I disease, while the other half had Hurley stage II disease. Their average AN count ranged between 5.3 and 5.6 — mostly inflammatory nodules and few abscesses. Patients were not allowed to receive any type of intervention or rescue therapy during the study.

Dr. Porter reported that the least square mean change in AN count from baseline to week 16 was -2.42 in the vehicle arm vs -3.61 in the ruxolitinib cream arm (P <.05). The proportion of patients who achieved a 50% decrease in AN count was 79.2% in the ruxolitinib cream arm, compared with 56.5% of patients in the vehicle arm, respectively. More patients in the ruxolitinib cream arm achieved a 75% decrease in AN count (54.2% vs 25%), a 90% decrease in AN count (20.8 vs 12.5%), and a 100% decrease in AN count (20.8% vs 12.5%).

In other findings, 79.2% of patients in the ruxolitinib cream arm achieved a Hidradenitis Suppurativa Clinical Response score from baseline through week 16, compared with 50% of those in the vehicle group. The International Hidradenitis Suppurativa Severity Score System results favored the ruxolitinib cream arm (-4.46 vs -2.66 in the vehicle arm). Skin Pain and Itch numeric rating scale scores were moderate at baseline and improved similarly in both groups during the study.

Ruxolitinib cream was generally well tolerated over 16 weeks. No serious treatment-emergent adverse events were reported. The most common adverse event reported in the ruxolitinib cream group was COVID-19 and nasopharyngitis (two cases each) and one case of an application site reaction.

“Twice-daily 1.5% ruxolitinib cream was effective in patients with milder HS,” Dr. Porter concluded. “Modifications to our traditionally accepted clinical endpoints may be needed in studies of patients with milder HS.”

Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, who was asked to comment on the results, characterized the study as exciting for several reasons.

“First, with the global push in recent years to increase HS awareness, I am already seeing more patients earlier in their disease course with milder disease, and there is currently a gap in approved therapies for this patient population,” she told this news organization.

“Second, patients are very interested in topical therapies for HS and are thrilled whenever they learn that topical options are under investigation. This study had small patient numbers, but it was encouraging to see the positive results for ruxolitinib cream and that the treatment appeared well-tolerated.”

The trial was sponsored by the Incyte Corporation. Dr. Porter disclosed that she has received consulting fees from AbbVie, Alumis, Eli Lilly, Incyte, Janssen, Novartis, Pfizer, Prometheus Laboratories, Sanofi, Sonoma Biotherapeutics, Trifecta Clinical, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com .

SAN DIEGO — Patients with mild hidradenitis suppurativa (HS) treated with ruxolitinib cream experienced a greater reduction in the abscess and inflammatory nodule (AN) count from baseline to week 16 than those who applied a vehicle cream, in a phase 2 trial.

“HS is a chronic, recurring inflammatory skin disease that is associated with painful inflammatory modules and abscesses,” said presenting author Martina J. Porter, MD, a dermatologist at Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts. Dr. Porter presented the data during a late-breaking session at the annual meeting of the American Academy of Dermatology.

“Over time, these patients may progress to having tunnels, ulcerations, malodorous discharge, and permanent scarring,” she said. “Currently, there are no approved therapies for milder HS, and the standard treatments that we apply in clinical practice are often inadequate.”

Ruxolitinib is a selective Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated efficacy in other inflammatory and autoimmune skin diseases. Ruxolitinib cream, 1.5%, is approved for treating mild to moderate atopic dermatitis and nonsegmental vitiligo in patients ages 12 years and older.

The phase 2 double-blind, vehicle-controlled trial evaluated the efficacy and safety of ruxolitinib cream for mild HS. Researchers assigned 69 adults with Hurley stage I or II HS to receive 1.5% ruxolitinib cream or vehicle cream twice daily for 16 weeks. The primary endpoint was the change from baseline in AN count at week 16. To be eligible, patients had to have an AN count between 3 and 10.

“This is much more mild than what we have seen in any systemic therapy trials,” Dr. Porter said. “And, if patients had 3 lesions, they all needed to be in one anatomic area, but if they had 4-10 lesions, they had to have two anatomic areas involved. Also, no patients with active draining tunnels were allowed in the study.”

Of the 69 patients, 34 received ruxolitinib cream and 35 received vehicle. About 51% of patients in the vehicle arm were Black and 34% were White, while about 32% of patients in the ruxolitinib arm were Black and 56% were White.

The mean age of patients overall was 29 years, and about half the patients in both study arms had Hurley stage I disease, while the other half had Hurley stage II disease. Their average AN count ranged between 5.3 and 5.6 — mostly inflammatory nodules and few abscesses. Patients were not allowed to receive any type of intervention or rescue therapy during the study.

Dr. Porter reported that the least square mean change in AN count from baseline to week 16 was -2.42 in the vehicle arm vs -3.61 in the ruxolitinib cream arm (P <.05). The proportion of patients who achieved a 50% decrease in AN count was 79.2% in the ruxolitinib cream arm, compared with 56.5% of patients in the vehicle arm, respectively. More patients in the ruxolitinib cream arm achieved a 75% decrease in AN count (54.2% vs 25%), a 90% decrease in AN count (20.8 vs 12.5%), and a 100% decrease in AN count (20.8% vs 12.5%).

In other findings, 79.2% of patients in the ruxolitinib cream arm achieved a Hidradenitis Suppurativa Clinical Response score from baseline through week 16, compared with 50% of those in the vehicle group. The International Hidradenitis Suppurativa Severity Score System results favored the ruxolitinib cream arm (-4.46 vs -2.66 in the vehicle arm). Skin Pain and Itch numeric rating scale scores were moderate at baseline and improved similarly in both groups during the study.

Ruxolitinib cream was generally well tolerated over 16 weeks. No serious treatment-emergent adverse events were reported. The most common adverse event reported in the ruxolitinib cream group was COVID-19 and nasopharyngitis (two cases each) and one case of an application site reaction.

“Twice-daily 1.5% ruxolitinib cream was effective in patients with milder HS,” Dr. Porter concluded. “Modifications to our traditionally accepted clinical endpoints may be needed in studies of patients with milder HS.”

Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, who was asked to comment on the results, characterized the study as exciting for several reasons.

“First, with the global push in recent years to increase HS awareness, I am already seeing more patients earlier in their disease course with milder disease, and there is currently a gap in approved therapies for this patient population,” she told this news organization.

“Second, patients are very interested in topical therapies for HS and are thrilled whenever they learn that topical options are under investigation. This study had small patient numbers, but it was encouraging to see the positive results for ruxolitinib cream and that the treatment appeared well-tolerated.”

The trial was sponsored by the Incyte Corporation. Dr. Porter disclosed that she has received consulting fees from AbbVie, Alumis, Eli Lilly, Incyte, Janssen, Novartis, Pfizer, Prometheus Laboratories, Sanofi, Sonoma Biotherapeutics, Trifecta Clinical, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com .

SAN DIEGO — Patients with mild hidradenitis suppurativa (HS) treated with ruxolitinib cream experienced a greater reduction in the abscess and inflammatory nodule (AN) count from baseline to week 16 than those who applied a vehicle cream, in a phase 2 trial.

“HS is a chronic, recurring inflammatory skin disease that is associated with painful inflammatory modules and abscesses,” said presenting author Martina J. Porter, MD, a dermatologist at Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts. Dr. Porter presented the data during a late-breaking session at the annual meeting of the American Academy of Dermatology.

“Over time, these patients may progress to having tunnels, ulcerations, malodorous discharge, and permanent scarring,” she said. “Currently, there are no approved therapies for milder HS, and the standard treatments that we apply in clinical practice are often inadequate.”

Ruxolitinib is a selective Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated efficacy in other inflammatory and autoimmune skin diseases. Ruxolitinib cream, 1.5%, is approved for treating mild to moderate atopic dermatitis and nonsegmental vitiligo in patients ages 12 years and older.

The phase 2 double-blind, vehicle-controlled trial evaluated the efficacy and safety of ruxolitinib cream for mild HS. Researchers assigned 69 adults with Hurley stage I or II HS to receive 1.5% ruxolitinib cream or vehicle cream twice daily for 16 weeks. The primary endpoint was the change from baseline in AN count at week 16. To be eligible, patients had to have an AN count between 3 and 10.

“This is much more mild than what we have seen in any systemic therapy trials,” Dr. Porter said. “And, if patients had 3 lesions, they all needed to be in one anatomic area, but if they had 4-10 lesions, they had to have two anatomic areas involved. Also, no patients with active draining tunnels were allowed in the study.”

Of the 69 patients, 34 received ruxolitinib cream and 35 received vehicle. About 51% of patients in the vehicle arm were Black and 34% were White, while about 32% of patients in the ruxolitinib arm were Black and 56% were White.

The mean age of patients overall was 29 years, and about half the patients in both study arms had Hurley stage I disease, while the other half had Hurley stage II disease. Their average AN count ranged between 5.3 and 5.6 — mostly inflammatory nodules and few abscesses. Patients were not allowed to receive any type of intervention or rescue therapy during the study.

Dr. Porter reported that the least square mean change in AN count from baseline to week 16 was -2.42 in the vehicle arm vs -3.61 in the ruxolitinib cream arm (P <.05). The proportion of patients who achieved a 50% decrease in AN count was 79.2% in the ruxolitinib cream arm, compared with 56.5% of patients in the vehicle arm, respectively. More patients in the ruxolitinib cream arm achieved a 75% decrease in AN count (54.2% vs 25%), a 90% decrease in AN count (20.8 vs 12.5%), and a 100% decrease in AN count (20.8% vs 12.5%).

In other findings, 79.2% of patients in the ruxolitinib cream arm achieved a Hidradenitis Suppurativa Clinical Response score from baseline through week 16, compared with 50% of those in the vehicle group. The International Hidradenitis Suppurativa Severity Score System results favored the ruxolitinib cream arm (-4.46 vs -2.66 in the vehicle arm). Skin Pain and Itch numeric rating scale scores were moderate at baseline and improved similarly in both groups during the study.

Ruxolitinib cream was generally well tolerated over 16 weeks. No serious treatment-emergent adverse events were reported. The most common adverse event reported in the ruxolitinib cream group was COVID-19 and nasopharyngitis (two cases each) and one case of an application site reaction.

“Twice-daily 1.5% ruxolitinib cream was effective in patients with milder HS,” Dr. Porter concluded. “Modifications to our traditionally accepted clinical endpoints may be needed in studies of patients with milder HS.”

Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, who was asked to comment on the results, characterized the study as exciting for several reasons.

“First, with the global push in recent years to increase HS awareness, I am already seeing more patients earlier in their disease course with milder disease, and there is currently a gap in approved therapies for this patient population,” she told this news organization.

“Second, patients are very interested in topical therapies for HS and are thrilled whenever they learn that topical options are under investigation. This study had small patient numbers, but it was encouraging to see the positive results for ruxolitinib cream and that the treatment appeared well-tolerated.”

The trial was sponsored by the Incyte Corporation. Dr. Porter disclosed that she has received consulting fees from AbbVie, Alumis, Eli Lilly, Incyte, Janssen, Novartis, Pfizer, Prometheus Laboratories, Sanofi, Sonoma Biotherapeutics, Trifecta Clinical, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com .

SAN DIEGO — A liquid biopsy assay that combines a microRNA signature and a well-known biomarker for pancreatic cancer has demonstrated an accuracy of 97% for detecting stage I/II pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer.

It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).

Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.

Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.

In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.

In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.

The test performed the same whether the tumor was in the head or tail of the pancreas.

“We are very excited about this data,” said Dr. Goel.

The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.

Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.

“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.

Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.

“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.

“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.

In the meantime, Dr. Goel said there’s more work to be done.

Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.

The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.

The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.

The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.

A version of this article appeared on Medscape.com.

SAN DIEGO — A liquid biopsy assay that combines a microRNA signature and a well-known biomarker for pancreatic cancer has demonstrated an accuracy of 97% for detecting stage I/II pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer.

It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).

Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.

Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.

In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.

In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.

The test performed the same whether the tumor was in the head or tail of the pancreas.

“We are very excited about this data,” said Dr. Goel.

The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.

Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.

“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.

Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.

“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.

“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.

In the meantime, Dr. Goel said there’s more work to be done.

Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.

The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.

The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.

The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.

A version of this article appeared on Medscape.com.

SAN DIEGO — A liquid biopsy assay that combines a microRNA signature and a well-known biomarker for pancreatic cancer has demonstrated an accuracy of 97% for detecting stage I/II pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer.

It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).

Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.

Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.

In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.

In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.

The test performed the same whether the tumor was in the head or tail of the pancreas.

“We are very excited about this data,” said Dr. Goel.

The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.

Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.

“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.

Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.

“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.

“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.

In the meantime, Dr. Goel said there’s more work to be done.

Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.

The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.

The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.

The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.

A version of this article appeared on Medscape.com.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.

The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.

“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.” 

The study findings were published online simultaneously in the Journal of the American College of Cardiology.
 

Telemedicine Protocol

The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter. 

Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years. 

If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.

Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.

Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).

MACE rates were similar between the two groups.

At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.

The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).

Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
 

Human Element Key

In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.

However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”

Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology. 

“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”

While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”

The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.

A version of this article first appeared on Medscape.com.

ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.

The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.

“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.” 

The study findings were published online simultaneously in the Journal of the American College of Cardiology.
 

Telemedicine Protocol

The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter. 

Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years. 

If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.

Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.

Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).

MACE rates were similar between the two groups.

At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.

The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).

Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
 

Human Element Key

In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.

However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”

Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology. 

“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”

While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”

The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.

A version of this article first appeared on Medscape.com.

ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.

The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.

“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.” 

The study findings were published online simultaneously in the Journal of the American College of Cardiology.
 

Telemedicine Protocol

The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter. 

Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years. 

If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.

Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.

Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).

MACE rates were similar between the two groups.

At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.

The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).

Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
 

Human Element Key

In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.

However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”

Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology. 

“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”

While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”

The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.