Hodgkin Lymphoma

The US Food and Drug Administration (FDA) has placed a partial hold on clinical trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The hold has halted enrollment in US-based trials of tazemetostat, but study subjects who have not experienced disease progression may continue to receive the drug.

The hold is due to an adverse event observed in a pediatric patient on a phase 1 study of tazemetostat.

The patient, who had advanced poorly differentiated chordoma, developed a secondary T-cell lymphoma while taking tazemetostat.

The patient had been on study for approximately 15 months and had achieved a confirmed partial response. Now, the patient has discontinued tazemetostat and is being treated for T-cell lymphoma.

More than 750 patients have been treated with tazemetostat to date, and this is the only case of secondary lymphoma that has been observed, according to Epizyme, Inc., the company developing tazemetostat.

The company also noted that doses of tazemetostat explored in its phase 1 pediatric study are higher than those used in the phase 2 adult studies.

Epizyme has begun taking steps to address the hold on tazemetostat trials—updating the informed consent, investigator’s brochure, and study protocols.

The company will need to confirm alignment with the FDA in order to resume US enrollment.

“We are working expeditiously with clinical trial investigators and regulatory authorities to initiate the appropriate steps to resume enrollment,” said Robert Bazemore, president and chief executive officer of Epizyme.

“Epizyme, along with our global investigator community, has been very encouraged by the clinical responses and tolerability of tazemetostat observed in pediatric and adult patients with hematological malignancies and solid tumors enrolled in our trials. We remain encouraged by the potential of tazemetostat to address the unmet needs of many patients living with cancer.”

The US Food and Drug Administration (FDA) has placed a partial hold on clinical trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The hold has halted enrollment in US-based trials of tazemetostat, but study subjects who have not experienced disease progression may continue to receive the drug.

The hold is due to an adverse event observed in a pediatric patient on a phase 1 study of tazemetostat.

The patient, who had advanced poorly differentiated chordoma, developed a secondary T-cell lymphoma while taking tazemetostat.

The patient had been on study for approximately 15 months and had achieved a confirmed partial response. Now, the patient has discontinued tazemetostat and is being treated for T-cell lymphoma.

More than 750 patients have been treated with tazemetostat to date, and this is the only case of secondary lymphoma that has been observed, according to Epizyme, Inc., the company developing tazemetostat.

The company also noted that doses of tazemetostat explored in its phase 1 pediatric study are higher than those used in the phase 2 adult studies.

Epizyme has begun taking steps to address the hold on tazemetostat trials—updating the informed consent, investigator’s brochure, and study protocols.

The company will need to confirm alignment with the FDA in order to resume US enrollment.

“We are working expeditiously with clinical trial investigators and regulatory authorities to initiate the appropriate steps to resume enrollment,” said Robert Bazemore, president and chief executive officer of Epizyme.

“Epizyme, along with our global investigator community, has been very encouraged by the clinical responses and tolerability of tazemetostat observed in pediatric and adult patients with hematological malignancies and solid tumors enrolled in our trials. We remain encouraged by the potential of tazemetostat to address the unmet needs of many patients living with cancer.”

The US Food and Drug Administration (FDA) has placed a partial hold on clinical trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The hold has halted enrollment in US-based trials of tazemetostat, but study subjects who have not experienced disease progression may continue to receive the drug.

The hold is due to an adverse event observed in a pediatric patient on a phase 1 study of tazemetostat.

The patient, who had advanced poorly differentiated chordoma, developed a secondary T-cell lymphoma while taking tazemetostat.

The patient had been on study for approximately 15 months and had achieved a confirmed partial response. Now, the patient has discontinued tazemetostat and is being treated for T-cell lymphoma.

More than 750 patients have been treated with tazemetostat to date, and this is the only case of secondary lymphoma that has been observed, according to Epizyme, Inc., the company developing tazemetostat.

The company also noted that doses of tazemetostat explored in its phase 1 pediatric study are higher than those used in the phase 2 adult studies.

Epizyme has begun taking steps to address the hold on tazemetostat trials—updating the informed consent, investigator’s brochure, and study protocols.

The company will need to confirm alignment with the FDA in order to resume US enrollment.

“We are working expeditiously with clinical trial investigators and regulatory authorities to initiate the appropriate steps to resume enrollment,” said Robert Bazemore, president and chief executive officer of Epizyme.

“Epizyme, along with our global investigator community, has been very encouraged by the clinical responses and tolerability of tazemetostat observed in pediatric and adult patients with hematological malignancies and solid tumors enrolled in our trials. We remain encouraged by the potential of tazemetostat to address the unmet needs of many patients living with cancer.”

Photo courtesy of CDC

New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.

The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.

After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.

Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.

The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.

The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).

Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.

Intervention

The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.

Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.

Results

The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.

After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).

Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).

In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.

Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.

All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.

The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.

Photo courtesy of CDC

New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.

The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.

After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.

Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.

The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.

The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).

Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.

Intervention

The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.

Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.

Results

The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.

After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).

Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).

In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.

Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.

All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.

The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.

Photo courtesy of CDC

New research suggests a bedside visual art intervention (BVAI) can reduce pain and anxiety in inpatients with hematologic malignancies, including those undergoing transplant.

The BVAI involved an educator teaching patients art technique one-on-one for approximately 30 minutes.

After a single session, patients had significant improvements in positive mood and pain scores, as well as decreases in negative mood and anxiety.

Alexandra P. Wolanskyj, MD, of Mayo Clinic in Rochester, Minnesota, and her colleagues reported these results in the European Journal of Cancer Care.

The study included 21 patients, 19 of them female. Their median age was 53.5 (range, 19-75). Six patients were undergoing hematopoietic stem cell transplant.

The patients had multiple myeloma (n=5), acute myeloid leukemia (n=5), non-Hodgkin lymphoma (n=3), Hodgkin lymphoma (n=2), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1), amyloidosis (n=1), Gardner-Diamond syndrome (n=1), myelodysplastic syndrome (n=1), and Waldenstrom’s macroglobulinemia (n=1).

Nearly half of patients had relapsed disease (47.6%), 23.8% had active and new disease, 19.0% had active disease with primary resistance on chemotherapy, and 9.5% of patients were in remission.

Intervention

The researchers recruited an educator from a community art center to teach art at the patients’ bedsides. Sessions were intended to be about 30 minutes. However, patients could stop at any time or continue beyond 30 minutes.

Patients and their families could make art or just observe. Materials used included watercolors, oil pastels, colored pencils, and clay (all non-toxic and odorless). The materials were left with patients so they could continue to use them after the sessions.

Results

The researchers assessed patients’ pain, anxiety, and mood at baseline and after the patients had a session with the art educator.

After the BVAI, patients had a significant decrease in pain, according to the Visual Analog Scale (VAS). The 14 patients who reported any pain at baseline had a mean reduction in VAS score of 1.5, or a 35.1% reduction in pain (P=0.017).

Patients had a 21.6% reduction in anxiety after the BVAI. Among the 20 patients who completed this assessment, there was a mean 9.2-point decrease in State-Trait Anxiety Inventory (STAI) score (P=0.001).

In addition, patients had a significant increase in positive mood and a significant decrease in negative mood after the BVAI. Mood was assessed in 20 patients using the Positive and Negative Affect Schedule (PANAS) scale.

Positive mood increased 14.6% (P=0.003), and negative mood decreased 18.0% (P=0.015) after the BVAI. Patients’ mean PANAS scores increased 4.6 points for positive mood and decreased 3.3 points for negative mood.

All 21 patients completed a questionnaire on the BVAI. All but 1 patient (95%) said the intervention was positive overall, and 85% of patients (n=18) said they would be interested in participating in future art-based interventions.

The researchers said these results suggest experiences provided by artists in the community may be an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

The Food and Drug Administration has approved brentuximab vedotin, in combination with chemotherapy, for previously untreated adults with stage III or IV classical Hodgkin lymphoma.

The drug, which is marketed by Seattle Genetics as Adcetris, is already approved in classical Hodgkin lymphoma after relapse and after stem cell transplant when the patient is at risk of relapse or progression. The drug is also approved to treat both systemic anaplastic large cell lymphoma (ALCL) and primary cutaneous ALCL after failure on other treatments.

[email protected]

The Food and Drug Administration has approved brentuximab vedotin, in combination with chemotherapy, for previously untreated adults with stage III or IV classical Hodgkin lymphoma.

The drug, which is marketed by Seattle Genetics as Adcetris, is already approved in classical Hodgkin lymphoma after relapse and after stem cell transplant when the patient is at risk of relapse or progression. The drug is also approved to treat both systemic anaplastic large cell lymphoma (ALCL) and primary cutaneous ALCL after failure on other treatments.

[email protected]

The Food and Drug Administration has approved brentuximab vedotin, in combination with chemotherapy, for previously untreated adults with stage III or IV classical Hodgkin lymphoma.

The drug, which is marketed by Seattle Genetics as Adcetris, is already approved in classical Hodgkin lymphoma after relapse and after stem cell transplant when the patient is at risk of relapse or progression. The drug is also approved to treat both systemic anaplastic large cell lymphoma (ALCL) and primary cutaneous ALCL after failure on other treatments.

[email protected]

Photo courtesy of CDC

ORLANDO—Results of a retrospective study showed that survivors of lymphoma or breast cancer had a significantly greater risk of congestive heart failure (CHF) than patients who did not have cancer.

This increased risk was observed as early as a year after cancer diagnosis but was still present 20 years after diagnosis.

Overall, 1 in 10 cancer patients had CHF at the 20-year mark.

“The majority of patients do not develop heart failure, but our research helps us recognize the factors associated with it and the importance of appropriate heart care following cancer treatment,” said Carolyn Larsen, MD, of the Mayo Clinic in Rochester, Minnesota.

“Our research suggests that periodic cardiac imaging to monitor for heart damage may be needed for some cancer patients, even if they have no signs of heart damage initially after chemotherapy. Additionally, it emphasizes that working to live a heart-healthy lifestyle is important for cancer patients and survivors to reduce the overall risk of heart disease.”

Dr Larsen and her colleagues presented this research as a poster (abstract 1105-066) at the American College of Cardiology’s 67th Annual Scientific Session & Expo (ACC.18).

Patients

Using data from the Rochester Epidemiology Project, the researchers retrospectively tracked CHF cases in 900 cancer patients and 1550 non-cancer patients. Patients were treated in Olmsted County in Minnesota from 1985 to 2010.

For both patient groups, the median age at baseline was about 53, a little more than 90% of each group was white, and nearly 80% of each group was female.

Six to 7% of patients had diabetes, and about 30% of each group had hypertension. Thirty-eight percent of each group had hyperlipidemia, and 31% were obese.

Five percent of cancer patients and 2% of controls had coronary artery disease (P<0.001). This was the only significant difference in baseline characteristics.

Cancer patients had been diagnosed with non-Hodgkin lymphoma (28%), Hodgkin lymphoma (9%), or breast cancer (64%). Forty-seven percent had received radiation, including right chest (21%), left chest (23%), and mediastinal (4%).

Eighty-four percent of patients had received anthracycline therapy. The median doxorubicin isotoxic dose was 240 mg/m².

At baseline, 12% of cancer patients were on beta-blockers, 8% were on angiotensin converting enzyme inhibitors, 4% were on angiotensin receptor blockers, and 11% were on statins.

Results

Cancer patients were more than 3 times as likely as controls to develop CHF. The hazard ratio (HR) was 3.6 (P<0.01) in an analysis adjusted for age, gender, diabetes, hypertension, coronary artery disease, dyslipidemia, and obesity at baseline.

The increased CHF risk among cancer patients was evident after the first year from cancer diagnosis and persisted at 20 years of follow-up.

“The risk of heart failure doesn’t go away after a couple of years,” Dr Larsen said. “It’s a long-term issue that patients need to discuss with their doctors and use as motivation to stay heart healthy.”

The incidence of CHF—in cancer patients and controls, respectively—was as follows:

• 1 year—1.5% vs 0.1%
• 5 years—3.1% vs 0.9%
• 10 years—5.0% vs 2%
• 20 years—10.1% vs 5.8%.

A multivariable analysis in the cancer patients revealed a few independent risk factors for CHF, including:

• Doxorubicin isotoxic dose ≥ 300 mg/m² (HR=2.34, P=0.003)
• Age at diagnosis (HR=3.06 for age ≥ 80 vs 60-69, P=0.01)
• Coronary artery disease at diagnosis (HR=2.27, P=0.04)
• Diabetes mellitus at diagnosis (HR=2.39, P<0.01).

Dr Larsen said additional research is needed to determine why diabetes carries a greater risk than other traditional risk factors, such as high blood pressure, in this group.

Mitigating risk

These findings raise important questions about what the appropriate surveillance should be for heart problems post-cancer treatment, Dr Larsen said. She believes more frequent cardiac imaging may be warranted in some patients to detect signs of CHF earlier.

“It’s an area that needs to be better defined,” Dr Larsen said. “An echocardiogram is usually done 6 to 12 months after cancer treatment with an anthracycline, but how often should it be done after that? We need to be more vigilant in making sure we try to prevent or control heart issues post-cancer care, especially in light of the growing appreciation of the connection between some cancer treatments and heart disease.”

Dr Larsen also noted that patients themselves can play a role in decreasing their risk of CHF, even if they are starting at a disadvantage.

A heart-healthy lifestyle—maintaining a normal body weight, regular exercise, and controlling other risk factors such as high blood pressure, diabetes, and high cholesterol—can help lower the risk of heart disease and CHF.

“If patients know they have received a drug treatment that might increase their risk of heart failure, it’s even more important to take care of the aspects of their life that they can control to reduce their risk as much as possible and to work with their medical care team to detect issues as early as possible,” Dr Larsen said.

Photo courtesy of CDC

ORLANDO—Results of a retrospective study showed that survivors of lymphoma or breast cancer had a significantly greater risk of congestive heart failure (CHF) than patients who did not have cancer.

This increased risk was observed as early as a year after cancer diagnosis but was still present 20 years after diagnosis.

Overall, 1 in 10 cancer patients had CHF at the 20-year mark.

“The majority of patients do not develop heart failure, but our research helps us recognize the factors associated with it and the importance of appropriate heart care following cancer treatment,” said Carolyn Larsen, MD, of the Mayo Clinic in Rochester, Minnesota.

“Our research suggests that periodic cardiac imaging to monitor for heart damage may be needed for some cancer patients, even if they have no signs of heart damage initially after chemotherapy. Additionally, it emphasizes that working to live a heart-healthy lifestyle is important for cancer patients and survivors to reduce the overall risk of heart disease.”

Dr Larsen and her colleagues presented this research as a poster (abstract 1105-066) at the American College of Cardiology’s 67th Annual Scientific Session & Expo (ACC.18).

Patients

Using data from the Rochester Epidemiology Project, the researchers retrospectively tracked CHF cases in 900 cancer patients and 1550 non-cancer patients. Patients were treated in Olmsted County in Minnesota from 1985 to 2010.

For both patient groups, the median age at baseline was about 53, a little more than 90% of each group was white, and nearly 80% of each group was female.

Six to 7% of patients had diabetes, and about 30% of each group had hypertension. Thirty-eight percent of each group had hyperlipidemia, and 31% were obese.

Five percent of cancer patients and 2% of controls had coronary artery disease (P<0.001). This was the only significant difference in baseline characteristics.

Cancer patients had been diagnosed with non-Hodgkin lymphoma (28%), Hodgkin lymphoma (9%), or breast cancer (64%). Forty-seven percent had received radiation, including right chest (21%), left chest (23%), and mediastinal (4%).

Eighty-four percent of patients had received anthracycline therapy. The median doxorubicin isotoxic dose was 240 mg/m².

At baseline, 12% of cancer patients were on beta-blockers, 8% were on angiotensin converting enzyme inhibitors, 4% were on angiotensin receptor blockers, and 11% were on statins.

Results

Cancer patients were more than 3 times as likely as controls to develop CHF. The hazard ratio (HR) was 3.6 (P<0.01) in an analysis adjusted for age, gender, diabetes, hypertension, coronary artery disease, dyslipidemia, and obesity at baseline.

The increased CHF risk among cancer patients was evident after the first year from cancer diagnosis and persisted at 20 years of follow-up.

“The risk of heart failure doesn’t go away after a couple of years,” Dr Larsen said. “It’s a long-term issue that patients need to discuss with their doctors and use as motivation to stay heart healthy.”

The incidence of CHF—in cancer patients and controls, respectively—was as follows:

• 1 year—1.5% vs 0.1%
• 5 years—3.1% vs 0.9%
• 10 years—5.0% vs 2%
• 20 years—10.1% vs 5.8%.

A multivariable analysis in the cancer patients revealed a few independent risk factors for CHF, including:

• Doxorubicin isotoxic dose ≥ 300 mg/m² (HR=2.34, P=0.003)
• Age at diagnosis (HR=3.06 for age ≥ 80 vs 60-69, P=0.01)
• Coronary artery disease at diagnosis (HR=2.27, P=0.04)
• Diabetes mellitus at diagnosis (HR=2.39, P<0.01).

Dr Larsen said additional research is needed to determine why diabetes carries a greater risk than other traditional risk factors, such as high blood pressure, in this group.

Mitigating risk

These findings raise important questions about what the appropriate surveillance should be for heart problems post-cancer treatment, Dr Larsen said. She believes more frequent cardiac imaging may be warranted in some patients to detect signs of CHF earlier.

“It’s an area that needs to be better defined,” Dr Larsen said. “An echocardiogram is usually done 6 to 12 months after cancer treatment with an anthracycline, but how often should it be done after that? We need to be more vigilant in making sure we try to prevent or control heart issues post-cancer care, especially in light of the growing appreciation of the connection between some cancer treatments and heart disease.”

Dr Larsen also noted that patients themselves can play a role in decreasing their risk of CHF, even if they are starting at a disadvantage.

A heart-healthy lifestyle—maintaining a normal body weight, regular exercise, and controlling other risk factors such as high blood pressure, diabetes, and high cholesterol—can help lower the risk of heart disease and CHF.

“If patients know they have received a drug treatment that might increase their risk of heart failure, it’s even more important to take care of the aspects of their life that they can control to reduce their risk as much as possible and to work with their medical care team to detect issues as early as possible,” Dr Larsen said.

Photo courtesy of CDC

ORLANDO—Results of a retrospective study showed that survivors of lymphoma or breast cancer had a significantly greater risk of congestive heart failure (CHF) than patients who did not have cancer.

This increased risk was observed as early as a year after cancer diagnosis but was still present 20 years after diagnosis.

Overall, 1 in 10 cancer patients had CHF at the 20-year mark.

“The majority of patients do not develop heart failure, but our research helps us recognize the factors associated with it and the importance of appropriate heart care following cancer treatment,” said Carolyn Larsen, MD, of the Mayo Clinic in Rochester, Minnesota.

“Our research suggests that periodic cardiac imaging to monitor for heart damage may be needed for some cancer patients, even if they have no signs of heart damage initially after chemotherapy. Additionally, it emphasizes that working to live a heart-healthy lifestyle is important for cancer patients and survivors to reduce the overall risk of heart disease.”

Dr Larsen and her colleagues presented this research as a poster (abstract 1105-066) at the American College of Cardiology’s 67th Annual Scientific Session & Expo (ACC.18).

Patients

Using data from the Rochester Epidemiology Project, the researchers retrospectively tracked CHF cases in 900 cancer patients and 1550 non-cancer patients. Patients were treated in Olmsted County in Minnesota from 1985 to 2010.

For both patient groups, the median age at baseline was about 53, a little more than 90% of each group was white, and nearly 80% of each group was female.

Six to 7% of patients had diabetes, and about 30% of each group had hypertension. Thirty-eight percent of each group had hyperlipidemia, and 31% were obese.

Five percent of cancer patients and 2% of controls had coronary artery disease (P<0.001). This was the only significant difference in baseline characteristics.

Cancer patients had been diagnosed with non-Hodgkin lymphoma (28%), Hodgkin lymphoma (9%), or breast cancer (64%). Forty-seven percent had received radiation, including right chest (21%), left chest (23%), and mediastinal (4%).

Eighty-four percent of patients had received anthracycline therapy. The median doxorubicin isotoxic dose was 240 mg/m².

At baseline, 12% of cancer patients were on beta-blockers, 8% were on angiotensin converting enzyme inhibitors, 4% were on angiotensin receptor blockers, and 11% were on statins.

Results

Cancer patients were more than 3 times as likely as controls to develop CHF. The hazard ratio (HR) was 3.6 (P<0.01) in an analysis adjusted for age, gender, diabetes, hypertension, coronary artery disease, dyslipidemia, and obesity at baseline.

The increased CHF risk among cancer patients was evident after the first year from cancer diagnosis and persisted at 20 years of follow-up.

“The risk of heart failure doesn’t go away after a couple of years,” Dr Larsen said. “It’s a long-term issue that patients need to discuss with their doctors and use as motivation to stay heart healthy.”

The incidence of CHF—in cancer patients and controls, respectively—was as follows:

• 1 year—1.5% vs 0.1%
• 5 years—3.1% vs 0.9%
• 10 years—5.0% vs 2%
• 20 years—10.1% vs 5.8%.

A multivariable analysis in the cancer patients revealed a few independent risk factors for CHF, including:

• Doxorubicin isotoxic dose ≥ 300 mg/m² (HR=2.34, P=0.003)
• Age at diagnosis (HR=3.06 for age ≥ 80 vs 60-69, P=0.01)
• Coronary artery disease at diagnosis (HR=2.27, P=0.04)
• Diabetes mellitus at diagnosis (HR=2.39, P<0.01).

Dr Larsen said additional research is needed to determine why diabetes carries a greater risk than other traditional risk factors, such as high blood pressure, in this group.

Mitigating risk

These findings raise important questions about what the appropriate surveillance should be for heart problems post-cancer treatment, Dr Larsen said. She believes more frequent cardiac imaging may be warranted in some patients to detect signs of CHF earlier.

“It’s an area that needs to be better defined,” Dr Larsen said. “An echocardiogram is usually done 6 to 12 months after cancer treatment with an anthracycline, but how often should it be done after that? We need to be more vigilant in making sure we try to prevent or control heart issues post-cancer care, especially in light of the growing appreciation of the connection between some cancer treatments and heart disease.”

Dr Larsen also noted that patients themselves can play a role in decreasing their risk of CHF, even if they are starting at a disadvantage.

A heart-healthy lifestyle—maintaining a normal body weight, regular exercise, and controlling other risk factors such as high blood pressure, diabetes, and high cholesterol—can help lower the risk of heart disease and CHF.

“If patients know they have received a drug treatment that might increase their risk of heart failure, it’s even more important to take care of the aspects of their life that they can control to reduce their risk as much as possible and to work with their medical care team to detect issues as early as possible,” Dr Larsen said.

Photo from Business Wire

The US Food and Drug Administration (FDA) has updated the label for nivolumab (Opdivo®) to include new dosing and administration information.

Nivolumab can now be given at 480 mg infused every 4 weeks for most approved indications, in addition to the previously approved dosing schedule of 240 mg every 2 weeks.

The FDA also approved a shorter 30-minute infusion across all approved indications of nivolumab.

The 480 mg dose option can be used for nearly all approved indications of nivolumab. The exceptions are patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.

Nivolumab is FDA-approved for the following indications:

• To treat adults with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT.
• As monotherapy for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma as well as BRAF V600 wild-type unresectable or metastatic melanoma.
• In combination with ipilimumab for the treatment of patients with unresectable or metastatic melanoma.
• To treat patients with metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab.
• For patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
• To treat patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy.
• For patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• To treat adult and pediatric (12 years and older) patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
• For patients with hepatocellular carcinoma who have been previously treated with sorafenib.
• For the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

Photo from Business Wire

The US Food and Drug Administration (FDA) has updated the label for nivolumab (Opdivo®) to include new dosing and administration information.

Nivolumab can now be given at 480 mg infused every 4 weeks for most approved indications, in addition to the previously approved dosing schedule of 240 mg every 2 weeks.

The FDA also approved a shorter 30-minute infusion across all approved indications of nivolumab.

The 480 mg dose option can be used for nearly all approved indications of nivolumab. The exceptions are patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.

Nivolumab is FDA-approved for the following indications:

• To treat adults with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT.
• As monotherapy for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma as well as BRAF V600 wild-type unresectable or metastatic melanoma.
• In combination with ipilimumab for the treatment of patients with unresectable or metastatic melanoma.
• To treat patients with metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab.
• For patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
• To treat patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy.
• For patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• To treat adult and pediatric (12 years and older) patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
• For patients with hepatocellular carcinoma who have been previously treated with sorafenib.
• For the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

Photo from Business Wire

The US Food and Drug Administration (FDA) has updated the label for nivolumab (Opdivo®) to include new dosing and administration information.

Nivolumab can now be given at 480 mg infused every 4 weeks for most approved indications, in addition to the previously approved dosing schedule of 240 mg every 2 weeks.

The FDA also approved a shorter 30-minute infusion across all approved indications of nivolumab.

The 480 mg dose option can be used for nearly all approved indications of nivolumab. The exceptions are patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.

Nivolumab is FDA-approved for the following indications:

• To treat adults with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT.
• As monotherapy for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma as well as BRAF V600 wild-type unresectable or metastatic melanoma.
• In combination with ipilimumab for the treatment of patients with unresectable or metastatic melanoma.
• To treat patients with metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab.
• For patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
• To treat patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy.
• For patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• To treat adult and pediatric (12 years and older) patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
• For patients with hepatocellular carcinoma who have been previously treated with sorafenib.
• For the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

Mitchell Horwitz, MD

SALT LAKE CITY—The expanded umbilical cord blood (UCB) product NiCord can be used as a stand-alone graft, according to research presented at the 2018 BMT Tandem Meetings.

Researchers found that a single NiCord unit provided “robust” engraftment in a phase 1/2 study of patients with high-risk hematologic malignancies.

NiCord recipients had quicker neutrophil and platelet engraftment than matched control subjects who received standard myeloablative UCB transplant (single or double).

Mitchell Horwitz, MD, of the Duke University Medical Center in Durham, North Carolina, presented these results at the meeting as abstract 49.* The research was sponsored by Gamida Cell, the company developing NiCord.

“[NiCord] is an ex vivo expanded cell product that’s derived from an entire unit of umbilical cord blood,” Dr Horwitz explained. “It’s manufactured starting with a CD133-positive selection, which is the progenitor cell population that’s cultured, and a T-cell containing CD133-negative fraction that is provided also at the time of transplant.”

“The culture system contains nicotinamide—that’s the active ingredient in the culture. And that’s supplemented with cytokines—thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor. The culture is 21 days.”

Previous research showed that double UCB transplant including a NiCord unit could provide benefits over standard double UCB transplant. This led Dr Horwitz and his colleagues to wonder if NiCord could be used as a stand-alone graft.

So the team evaluated the safety and efficacy of NiCord alone in 36 adolescents/adults with high-risk hematologic malignancies.

Patients had acute myelogenous leukemia (n=17), acute lymphoblastic leukemia (n=9), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=2), and Hodgkin lymphoma (n=1).

Most patients had intermediate (n=15) or high-risk (n=13) disease. They had a median age of 44 (range, 13-63) and a median weight of 75 kg (range, 41-125).

Treatment

For conditioning, 19 patients received thiotepa, busulfan, and fludarabine. Fifteen patients received total body irradiation and fludarabine with or without cyclophosphamide or thiotepa. And 2 patients received clofarabine, fludarabine, and busulfan.

Most patients had a 4/6 human leukocyte antigen (HLA) match (n=26), 8 had a 5/6 HLA match, and 2 had a 6/6 HLA match.

The median total nucleated cell dose was 2.4 x 10⁷/kg prior to expansion of the UCB unit and 3.7 x 10⁷/kg after expansion. The median CD34+ cell dose was 0.2 x 10⁶/kg and 6.3 x 10⁶/kg, respectively.

“CD34 cells were expanded 33-fold in the 3-week culture system,” Dr Horwitz noted. “That translated to a median CD34 dose of 6.3 x 10⁶/kg, a dose comparable to what would be obtained from an adult donor graft.”

Engraftment

There was 1 case of primary graft failure and 2 cases of secondary graft failure. One case of secondary graft failure was associated with an HHV-6 infection, and the other was due to a lethal adenovirus infection.

Of those patients who engrafted, 97% achieved full donor chimerism, and 3% had mixed chimerism.

Dr Horwitz and his colleagues compared engraftment results in the NiCord recipients to results in a cohort of patients from the CIBMTR registry who underwent UCB transplants from 2010 to 2013. They had similar characteristics as the NiCord patients—age, conditioning regimen, disease status, etc.

In total, there were 148 CIBMTR registry patients, 20% of whom received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the CIBMTR matched control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the CIBMTR controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

“There’s a median 10-day reduction in neutrophil recovery [and] 12-day reduction in time to platelet recovery [with NiCord],” Dr Horwitz noted. “There is evidence of robust and durable engraftment with a NiCord unit, with one patient now over 7 years from his first transplant on the pilot trial.”

Relapse, survival, and GVHD

Dr Horwitz reported other outcomes in the NiCord recipients without making comparisons to the CIBMTR matched controls.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the estimated 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The estimated overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute GVHD was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%.

The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the estimated 2-year rate of moderate to severe chronic GVHD was 9.8%.

Dr Horwitz said these “promising results” have led to the launch of a phase 3 registration trial in which researchers are comparing NiCord to standard single or double UCB transplant. The trial is open for accrual.

*Information in the abstract differs from the presentation.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.