Conference Coverage

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO — A new blood test that combines cell-free DNA fragmentomes and protein biomarkers to screen for ovarian cancer shows promising results, according to an initial analysis. 

The test, under development by Delfi Diagnostics, “looks very sensitive for detecting ovarian cancer early,” said company founder and board member Victor E. Velculescu, MD, PhD, codirector of Cancer Genetics and Epigenetics at Johns Hopkins University, Baltimore. 

The assay uses machine learning to integrate cell-free DNA fragment patterns with concentrations of two ovarian cancer biomarkers — CA125 and HE4 — to detect tumors. 

While fragmentation patterns are organized in healthy people, they are chaotic in cancer and reveal both its presence and location, said Velculescu who presented the findings at the American Association for Cancer Research annual meeting.

The researchers tested the assay in 134 women with ovarian cancer, 204 women without cancer, and 203 women with benign adnexal masses. The approach identified 69% of stage 1 cancers, 76% of stage 2, 85% of stage 3, and 100% of stage 4 at a specificity of over 99% and an area under the curve (AUC) of 0.97.

The test identified 91% of high-grade serous ovarian cancers — the most common type of ovarian cancer.

The AUC for distinguishing benign masses from cancer was 0.87, with 60% of ovarian cancers detected at a specificity of 95%. 

“In the preoperative setting where lower specificity is acceptable, this approach may improve management of adnexal masses,” the investigators said in their abstract.

Dr. Velculescu cautioned that the report “is an initial analysis” and that his team is working on validating the finding on a larger scale in both average and high-risk women.

If validated, the test “could enable population-wide ovarian cancer screening,” he added.

Delfi recently launched a lung cancer screening blood test — FirstLook Lung— that also uses a “fragmentomics” approach to detect tumors. The company is hopeful it will reach the market with a similar test for ovarian cancer, but it’s not a certainty. 

With lung cancer, we know screening helps. For ovarian cancer, however, it’s unclear whether this will help or not, said Dr. Velculescu. But based on the study findings, but “we are now optimistic that this could make an impact. We have more work to do.” 

This presentation was one of many at the meeting about liquid biopsies using DNA, RNA, and proteins to detect cancer, including a new assay for pancreatic cancer, another cancer that like ovarian cancer is difficult to detect in the early stages. 

“This is the future,” said study moderator Roy S. Herbst, MD, PhD, chief of medical oncology at Yale University in New Haven, Connecticut. 

He called liquid biopsy “a great advance” in many oncology settings, including cancer screening because finding tumors early offers the best chance at cure. 

However, one of the main concerns about rolling out liquid biopsies for wide-scale cancer screening is the possibility that a test will come back positive, but no tumor will be seen on diagnostic imaging, said Herbst. It won’t be clear if the test was a false positive or if the patient has a brewing tumor that can’t be located and treated, a difficult situation for both patients and doctors. 

What to do in that situation is “a policy question that the entire country is asking now as liquid biopsies are moving forward,” he said. We are going to have to come together to figure it out and learn how to use these tests.

The work was funded by Delfi Diagnostics, the National Institutes of Health, and others. Dr. Velculescu, in addition to founding Delfi, holds patents on the technology. Dr. Herbst is a consultant, researcher, and/or holds stock in many companies, including AstraZeneca, Pfizer, and Checkpoint Therapeutics. 
 

A version of this article appeared on Medscape.com .

SAN DIEGO — A new blood test that combines cell-free DNA fragmentomes and protein biomarkers to screen for ovarian cancer shows promising results, according to an initial analysis. 

The test, under development by Delfi Diagnostics, “looks very sensitive for detecting ovarian cancer early,” said company founder and board member Victor E. Velculescu, MD, PhD, codirector of Cancer Genetics and Epigenetics at Johns Hopkins University, Baltimore. 

The assay uses machine learning to integrate cell-free DNA fragment patterns with concentrations of two ovarian cancer biomarkers — CA125 and HE4 — to detect tumors. 

While fragmentation patterns are organized in healthy people, they are chaotic in cancer and reveal both its presence and location, said Velculescu who presented the findings at the American Association for Cancer Research annual meeting.

The researchers tested the assay in 134 women with ovarian cancer, 204 women without cancer, and 203 women with benign adnexal masses. The approach identified 69% of stage 1 cancers, 76% of stage 2, 85% of stage 3, and 100% of stage 4 at a specificity of over 99% and an area under the curve (AUC) of 0.97.

The test identified 91% of high-grade serous ovarian cancers — the most common type of ovarian cancer.

The AUC for distinguishing benign masses from cancer was 0.87, with 60% of ovarian cancers detected at a specificity of 95%. 

“In the preoperative setting where lower specificity is acceptable, this approach may improve management of adnexal masses,” the investigators said in their abstract.

Dr. Velculescu cautioned that the report “is an initial analysis” and that his team is working on validating the finding on a larger scale in both average and high-risk women.

If validated, the test “could enable population-wide ovarian cancer screening,” he added.

Delfi recently launched a lung cancer screening blood test — FirstLook Lung— that also uses a “fragmentomics” approach to detect tumors. The company is hopeful it will reach the market with a similar test for ovarian cancer, but it’s not a certainty. 

With lung cancer, we know screening helps. For ovarian cancer, however, it’s unclear whether this will help or not, said Dr. Velculescu. But based on the study findings, but “we are now optimistic that this could make an impact. We have more work to do.” 

This presentation was one of many at the meeting about liquid biopsies using DNA, RNA, and proteins to detect cancer, including a new assay for pancreatic cancer, another cancer that like ovarian cancer is difficult to detect in the early stages. 

“This is the future,” said study moderator Roy S. Herbst, MD, PhD, chief of medical oncology at Yale University in New Haven, Connecticut. 

He called liquid biopsy “a great advance” in many oncology settings, including cancer screening because finding tumors early offers the best chance at cure. 

However, one of the main concerns about rolling out liquid biopsies for wide-scale cancer screening is the possibility that a test will come back positive, but no tumor will be seen on diagnostic imaging, said Herbst. It won’t be clear if the test was a false positive or if the patient has a brewing tumor that can’t be located and treated, a difficult situation for both patients and doctors. 

What to do in that situation is “a policy question that the entire country is asking now as liquid biopsies are moving forward,” he said. We are going to have to come together to figure it out and learn how to use these tests.

The work was funded by Delfi Diagnostics, the National Institutes of Health, and others. Dr. Velculescu, in addition to founding Delfi, holds patents on the technology. Dr. Herbst is a consultant, researcher, and/or holds stock in many companies, including AstraZeneca, Pfizer, and Checkpoint Therapeutics. 
 

A version of this article appeared on Medscape.com .

SAN DIEGO — A new blood test that combines cell-free DNA fragmentomes and protein biomarkers to screen for ovarian cancer shows promising results, according to an initial analysis. 

The test, under development by Delfi Diagnostics, “looks very sensitive for detecting ovarian cancer early,” said company founder and board member Victor E. Velculescu, MD, PhD, codirector of Cancer Genetics and Epigenetics at Johns Hopkins University, Baltimore. 

The assay uses machine learning to integrate cell-free DNA fragment patterns with concentrations of two ovarian cancer biomarkers — CA125 and HE4 — to detect tumors. 

While fragmentation patterns are organized in healthy people, they are chaotic in cancer and reveal both its presence and location, said Velculescu who presented the findings at the American Association for Cancer Research annual meeting.

The researchers tested the assay in 134 women with ovarian cancer, 204 women without cancer, and 203 women with benign adnexal masses. The approach identified 69% of stage 1 cancers, 76% of stage 2, 85% of stage 3, and 100% of stage 4 at a specificity of over 99% and an area under the curve (AUC) of 0.97.

The test identified 91% of high-grade serous ovarian cancers — the most common type of ovarian cancer.

The AUC for distinguishing benign masses from cancer was 0.87, with 60% of ovarian cancers detected at a specificity of 95%. 

“In the preoperative setting where lower specificity is acceptable, this approach may improve management of adnexal masses,” the investigators said in their abstract.

Dr. Velculescu cautioned that the report “is an initial analysis” and that his team is working on validating the finding on a larger scale in both average and high-risk women.

If validated, the test “could enable population-wide ovarian cancer screening,” he added.

Delfi recently launched a lung cancer screening blood test — FirstLook Lung— that also uses a “fragmentomics” approach to detect tumors. The company is hopeful it will reach the market with a similar test for ovarian cancer, but it’s not a certainty. 

With lung cancer, we know screening helps. For ovarian cancer, however, it’s unclear whether this will help or not, said Dr. Velculescu. But based on the study findings, but “we are now optimistic that this could make an impact. We have more work to do.” 

This presentation was one of many at the meeting about liquid biopsies using DNA, RNA, and proteins to detect cancer, including a new assay for pancreatic cancer, another cancer that like ovarian cancer is difficult to detect in the early stages. 

“This is the future,” said study moderator Roy S. Herbst, MD, PhD, chief of medical oncology at Yale University in New Haven, Connecticut. 

He called liquid biopsy “a great advance” in many oncology settings, including cancer screening because finding tumors early offers the best chance at cure. 

However, one of the main concerns about rolling out liquid biopsies for wide-scale cancer screening is the possibility that a test will come back positive, but no tumor will be seen on diagnostic imaging, said Herbst. It won’t be clear if the test was a false positive or if the patient has a brewing tumor that can’t be located and treated, a difficult situation for both patients and doctors. 

What to do in that situation is “a policy question that the entire country is asking now as liquid biopsies are moving forward,” he said. We are going to have to come together to figure it out and learn how to use these tests.

The work was funded by Delfi Diagnostics, the National Institutes of Health, and others. Dr. Velculescu, in addition to founding Delfi, holds patents on the technology. Dr. Herbst is a consultant, researcher, and/or holds stock in many companies, including AstraZeneca, Pfizer, and Checkpoint Therapeutics. 
 

A version of this article appeared on Medscape.com .

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.