Lymphoma & Plasma Cell Disorders

For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), adding polatuzumab vedotin to bendamustine and rituximab can improve complete response rates and extend overall survival, according to findings from a phase 1b/2 trial.

Adding polatuzumab decreased mortality risk by 58%, reported lead author Laurie H. Sehn, MD, of the University of British Columbia, Vancouver, and colleagues.

Combination therapy with polatuzumab, bendamustine, and rituximab “represents a novel, effective therapeutic regimen to address the unmet need of patients with transplantation-ineligible [relapsed/refractory] DLBCL,” the investigators wrote. Since just 25% of polatuzumab combination–treated patients had received prior autologous stem cell transplant, the investigators said they could not make definitive conclusions on this combination’s efficacy in the post-ASCT setting.

Additional trials involving polatuzumab in the relapsed/refractory setting are ongoing. For patients with treatment-naive DLBCL, a phase 3 trial (NCT03274492) is evaluating substitution of polatuzumab for vincristine in the R-CHOP regimen.

The study was funded by F. Hoffmann-La Roche and Genentech. The investigators reported additional relationships with AbbVie, Kite Pharma, Lundbeck, and others.

SOURCE: Sehn LH et al. J Clin Oncol. 2019 Nov 6. doi: 10.1200/JCO.19.00172.

For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), adding polatuzumab vedotin to bendamustine and rituximab can improve complete response rates and extend overall survival, according to findings from a phase 1b/2 trial.

Adding polatuzumab decreased mortality risk by 58%, reported lead author Laurie H. Sehn, MD, of the University of British Columbia, Vancouver, and colleagues.

Combination therapy with polatuzumab, bendamustine, and rituximab “represents a novel, effective therapeutic regimen to address the unmet need of patients with transplantation-ineligible [relapsed/refractory] DLBCL,” the investigators wrote. Since just 25% of polatuzumab combination–treated patients had received prior autologous stem cell transplant, the investigators said they could not make definitive conclusions on this combination’s efficacy in the post-ASCT setting.

Additional trials involving polatuzumab in the relapsed/refractory setting are ongoing. For patients with treatment-naive DLBCL, a phase 3 trial (NCT03274492) is evaluating substitution of polatuzumab for vincristine in the R-CHOP regimen.

The study was funded by F. Hoffmann-La Roche and Genentech. The investigators reported additional relationships with AbbVie, Kite Pharma, Lundbeck, and others.

SOURCE: Sehn LH et al. J Clin Oncol. 2019 Nov 6. doi: 10.1200/JCO.19.00172.

For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), adding polatuzumab vedotin to bendamustine and rituximab can improve complete response rates and extend overall survival, according to findings from a phase 1b/2 trial.

Adding polatuzumab decreased mortality risk by 58%, reported lead author Laurie H. Sehn, MD, of the University of British Columbia, Vancouver, and colleagues.

Combination therapy with polatuzumab, bendamustine, and rituximab “represents a novel, effective therapeutic regimen to address the unmet need of patients with transplantation-ineligible [relapsed/refractory] DLBCL,” the investigators wrote. Since just 25% of polatuzumab combination–treated patients had received prior autologous stem cell transplant, the investigators said they could not make definitive conclusions on this combination’s efficacy in the post-ASCT setting.

Additional trials involving polatuzumab in the relapsed/refractory setting are ongoing. For patients with treatment-naive DLBCL, a phase 3 trial (NCT03274492) is evaluating substitution of polatuzumab for vincristine in the R-CHOP regimen.

The study was funded by F. Hoffmann-La Roche and Genentech. The investigators reported additional relationships with AbbVie, Kite Pharma, Lundbeck, and others.

SOURCE: Sehn LH et al. J Clin Oncol. 2019 Nov 6. doi: 10.1200/JCO.19.00172.

The Food and Drug Administration has approved zanubrutinib (Brukinsa) for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy.

Olivier Le Moal/Getty Images

The approval is based on results from two separate studies; in a global phase 1/2 trial, patients with relapsed or refractory MCL who received zanubrutinib had an overall response rate of 84%, with 22% experiencing a complete response and 62% experiencing partial response. Median duration of response was 18.5 months. The ORR in the second study – a multicenter phase 2 trial – was also 84%, but with 59% experiencing a complete response and 24% experiencing partial response; duration of response was 19.5 months.

The most common adverse events reported during the trials were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, hematuria, fatigue, constipation, and hemorrhage. The most common serious adverse events were pneumonia and hemorrhage.

Of the 118 patients with MCL treated with zanubrutinib over the two trials, 8 had to be discontinued because of adverse events.

The recommended dose of zanubrutinib is 320 mg, taken orally 160 mg twice daily or 320 mg once daily, with or without food.

“BTK [Bruton kinase] inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects. Today we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL,” Luhua (Michael) Wang, MD, clinical trial investigator and professor in the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, said in a statement.

[email protected]

The Food and Drug Administration has approved zanubrutinib (Brukinsa) for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy.

Olivier Le Moal/Getty Images

The approval is based on results from two separate studies; in a global phase 1/2 trial, patients with relapsed or refractory MCL who received zanubrutinib had an overall response rate of 84%, with 22% experiencing a complete response and 62% experiencing partial response. Median duration of response was 18.5 months. The ORR in the second study – a multicenter phase 2 trial – was also 84%, but with 59% experiencing a complete response and 24% experiencing partial response; duration of response was 19.5 months.

The most common adverse events reported during the trials were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, hematuria, fatigue, constipation, and hemorrhage. The most common serious adverse events were pneumonia and hemorrhage.

Of the 118 patients with MCL treated with zanubrutinib over the two trials, 8 had to be discontinued because of adverse events.

The recommended dose of zanubrutinib is 320 mg, taken orally 160 mg twice daily or 320 mg once daily, with or without food.

“BTK [Bruton kinase] inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects. Today we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL,” Luhua (Michael) Wang, MD, clinical trial investigator and professor in the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, said in a statement.

[email protected]

The Food and Drug Administration has approved zanubrutinib (Brukinsa) for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy.

Olivier Le Moal/Getty Images

The approval is based on results from two separate studies; in a global phase 1/2 trial, patients with relapsed or refractory MCL who received zanubrutinib had an overall response rate of 84%, with 22% experiencing a complete response and 62% experiencing partial response. Median duration of response was 18.5 months. The ORR in the second study – a multicenter phase 2 trial – was also 84%, but with 59% experiencing a complete response and 24% experiencing partial response; duration of response was 19.5 months.

The most common adverse events reported during the trials were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, hematuria, fatigue, constipation, and hemorrhage. The most common serious adverse events were pneumonia and hemorrhage.

Of the 118 patients with MCL treated with zanubrutinib over the two trials, 8 had to be discontinued because of adverse events.

The recommended dose of zanubrutinib is 320 mg, taken orally 160 mg twice daily or 320 mg once daily, with or without food.

“BTK [Bruton kinase] inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects. Today we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL,” Luhua (Michael) Wang, MD, clinical trial investigator and professor in the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, said in a statement.

[email protected]

A novel 17-gene expression signature may help guide the choice of initial treatment in patients with IGHV-unmutated chronic lymphocytic leukemia (CLL), according to findings of a retrospective dual cohort study.

copyright Kativ/iStockphoto

“[Fludarabine, cyclophosphamide, and rituximab] was the first regimen to improve progression-free survival and overall survival in patients with chronic lymphocytic leukaemia, and has become a gold-standard chemoimmunotherapy regimen in physically fit patients,” wrote the investigators, who were led by Carmen D. Herling, MD, of the Center for Integrated Oncology, Cologne, Germany; and Kevin R. Coombes, PhD, of Ohio State University, Columbus.

While several studies demonstrate that young, fit patients with mutated IGHV gene and no high-risk cytogenetic abnormalities achieve durable remission with the FCR (fludarabine, cyclophosphamide, and rituximab) regimen, there have been no studies to identify if this is true for patients with unmutated IGHV gene, they reported in the Lancet Oncology.

The investigators performed transcriptional profiling using peripheral blood samples collected from two cohorts of patients with CLL who were treated with frontline FCR.

The discovery and training cohort consisted of 101 patients (65% with IGHV-unmutated disease) treated at the MD Anderson Cancer Center who had a median follow-up of about 12 years. The validation cohort consisted of 109 patients with IGHV-unmutated disease treated on the German CLL8 single-arm trial who had a median follow-up of about 6 years.

A total of 1,136 genes showed a significant univariate association with time to progression. Ultimately, 17 of these genes – most of them involved in purine metabolism and oxidative phosphorylation – were included in the expression signature.

Among patients with IGHV-unmutated CLL, the 17-gene signature discriminated between two groups having differing time to progression after their frontline FCR chemoimmunotherapy: an unfavorable prognosis group and an intermediate prognosis group.

The unfavorable prognosis group had a significantly higher relative risk of progression in both the discovery/training cohort (hazard ratio, 3.83; P less than .0001) and the validation cohort (HR, 1.90; P = .008). In the validation cohort, the median time to progression was 39 months among patients with a signature-defined unfavorable prognosis, compared with 59 months among patients with a signature-defined intermediate prognosis.

“We would recommend testing the value of the 17-gene signature in a prospective study that compares FCR treatment with alternative therapies, such as ibrutinib, as part of a randomised clinical trial,” the investigators wrote.

Dr. Herling reported financial disclosures related to Hoffmann-La Roche, and Dr. Coombes reported grants from the National Institutes of Health. The study was funded by the Chronic Lymphocytic Leukaemia Global Research Foundation and the National Institutes of Health/National Cancer Institute.

SOURCE: Herling CD et al. Lancet Oncol. 2019;20(11):1576-86.

A novel 17-gene expression signature may help guide the choice of initial treatment in patients with IGHV-unmutated chronic lymphocytic leukemia (CLL), according to findings of a retrospective dual cohort study.

copyright Kativ/iStockphoto

“[Fludarabine, cyclophosphamide, and rituximab] was the first regimen to improve progression-free survival and overall survival in patients with chronic lymphocytic leukaemia, and has become a gold-standard chemoimmunotherapy regimen in physically fit patients,” wrote the investigators, who were led by Carmen D. Herling, MD, of the Center for Integrated Oncology, Cologne, Germany; and Kevin R. Coombes, PhD, of Ohio State University, Columbus.

While several studies demonstrate that young, fit patients with mutated IGHV gene and no high-risk cytogenetic abnormalities achieve durable remission with the FCR (fludarabine, cyclophosphamide, and rituximab) regimen, there have been no studies to identify if this is true for patients with unmutated IGHV gene, they reported in the Lancet Oncology.

The investigators performed transcriptional profiling using peripheral blood samples collected from two cohorts of patients with CLL who were treated with frontline FCR.

The discovery and training cohort consisted of 101 patients (65% with IGHV-unmutated disease) treated at the MD Anderson Cancer Center who had a median follow-up of about 12 years. The validation cohort consisted of 109 patients with IGHV-unmutated disease treated on the German CLL8 single-arm trial who had a median follow-up of about 6 years.

A total of 1,136 genes showed a significant univariate association with time to progression. Ultimately, 17 of these genes – most of them involved in purine metabolism and oxidative phosphorylation – were included in the expression signature.

Among patients with IGHV-unmutated CLL, the 17-gene signature discriminated between two groups having differing time to progression after their frontline FCR chemoimmunotherapy: an unfavorable prognosis group and an intermediate prognosis group.

The unfavorable prognosis group had a significantly higher relative risk of progression in both the discovery/training cohort (hazard ratio, 3.83; P less than .0001) and the validation cohort (HR, 1.90; P = .008). In the validation cohort, the median time to progression was 39 months among patients with a signature-defined unfavorable prognosis, compared with 59 months among patients with a signature-defined intermediate prognosis.

“We would recommend testing the value of the 17-gene signature in a prospective study that compares FCR treatment with alternative therapies, such as ibrutinib, as part of a randomised clinical trial,” the investigators wrote.

Dr. Herling reported financial disclosures related to Hoffmann-La Roche, and Dr. Coombes reported grants from the National Institutes of Health. The study was funded by the Chronic Lymphocytic Leukaemia Global Research Foundation and the National Institutes of Health/National Cancer Institute.

SOURCE: Herling CD et al. Lancet Oncol. 2019;20(11):1576-86.

A novel 17-gene expression signature may help guide the choice of initial treatment in patients with IGHV-unmutated chronic lymphocytic leukemia (CLL), according to findings of a retrospective dual cohort study.

copyright Kativ/iStockphoto

“[Fludarabine, cyclophosphamide, and rituximab] was the first regimen to improve progression-free survival and overall survival in patients with chronic lymphocytic leukaemia, and has become a gold-standard chemoimmunotherapy regimen in physically fit patients,” wrote the investigators, who were led by Carmen D. Herling, MD, of the Center for Integrated Oncology, Cologne, Germany; and Kevin R. Coombes, PhD, of Ohio State University, Columbus.

While several studies demonstrate that young, fit patients with mutated IGHV gene and no high-risk cytogenetic abnormalities achieve durable remission with the FCR (fludarabine, cyclophosphamide, and rituximab) regimen, there have been no studies to identify if this is true for patients with unmutated IGHV gene, they reported in the Lancet Oncology.

The investigators performed transcriptional profiling using peripheral blood samples collected from two cohorts of patients with CLL who were treated with frontline FCR.

The discovery and training cohort consisted of 101 patients (65% with IGHV-unmutated disease) treated at the MD Anderson Cancer Center who had a median follow-up of about 12 years. The validation cohort consisted of 109 patients with IGHV-unmutated disease treated on the German CLL8 single-arm trial who had a median follow-up of about 6 years.

A total of 1,136 genes showed a significant univariate association with time to progression. Ultimately, 17 of these genes – most of them involved in purine metabolism and oxidative phosphorylation – were included in the expression signature.

Among patients with IGHV-unmutated CLL, the 17-gene signature discriminated between two groups having differing time to progression after their frontline FCR chemoimmunotherapy: an unfavorable prognosis group and an intermediate prognosis group.

The unfavorable prognosis group had a significantly higher relative risk of progression in both the discovery/training cohort (hazard ratio, 3.83; P less than .0001) and the validation cohort (HR, 1.90; P = .008). In the validation cohort, the median time to progression was 39 months among patients with a signature-defined unfavorable prognosis, compared with 59 months among patients with a signature-defined intermediate prognosis.

“We would recommend testing the value of the 17-gene signature in a prospective study that compares FCR treatment with alternative therapies, such as ibrutinib, as part of a randomised clinical trial,” the investigators wrote.

Dr. Herling reported financial disclosures related to Hoffmann-La Roche, and Dr. Coombes reported grants from the National Institutes of Health. The study was funded by the Chronic Lymphocytic Leukaemia Global Research Foundation and the National Institutes of Health/National Cancer Institute.

SOURCE: Herling CD et al. Lancet Oncol. 2019;20(11):1576-86.

The Multiple Myeloma Research Foundation (MMRF) recently launched its Direct-to-Patient registry, in what the organization’s leaders are describing as a “disruptive” step toward improving outcomes for patients with multiple myeloma.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

The new registry is intended to build upon CoMMpass, a program started 8 years ago that now represents the largest genomic database of any type of cancer. Although CoMMpass includes data from about 1,150 patients with myeloma, it’s not enough information, according to the chief marketing and development officer at the MMRF, Anne Quinn Young.

“For a disease as heterogenous as myeloma is, we need more, particularly because we don’t have all the samples for later-stage disease,” Ms. Quinn Young said in an interview. “And even with the clinical data, given the patient population, both [in terms of] demographics and the nature of the disease, the numbers of patients still living after multiple relapses is rather small.”

In an earlier effort to gather more data, the MMRF first turned to other organizations for help, but this approach fell short because of scarcity of data, and in some cases, unwillingness to share. Steven Labkoff, MD, chief data officer at the MMRF, described this experience in an interview.

The Multiple Myeloma Research Foundation (MMRF) recently launched its Direct-to-Patient registry, in what the organization’s leaders are describing as a “disruptive” step toward improving outcomes for patients with multiple myeloma.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

The new registry is intended to build upon CoMMpass, a program started 8 years ago that now represents the largest genomic database of any type of cancer. Although CoMMpass includes data from about 1,150 patients with myeloma, it’s not enough information, according to the chief marketing and development officer at the MMRF, Anne Quinn Young.

“For a disease as heterogenous as myeloma is, we need more, particularly because we don’t have all the samples for later-stage disease,” Ms. Quinn Young said in an interview. “And even with the clinical data, given the patient population, both [in terms of] demographics and the nature of the disease, the numbers of patients still living after multiple relapses is rather small.”

In an earlier effort to gather more data, the MMRF first turned to other organizations for help, but this approach fell short because of scarcity of data, and in some cases, unwillingness to share. Steven Labkoff, MD, chief data officer at the MMRF, described this experience in an interview.

The Multiple Myeloma Research Foundation (MMRF) recently launched its Direct-to-Patient registry, in what the organization’s leaders are describing as a “disruptive” step toward improving outcomes for patients with multiple myeloma.

Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology

The new registry is intended to build upon CoMMpass, a program started 8 years ago that now represents the largest genomic database of any type of cancer. Although CoMMpass includes data from about 1,150 patients with myeloma, it’s not enough information, according to the chief marketing and development officer at the MMRF, Anne Quinn Young.

“For a disease as heterogenous as myeloma is, we need more, particularly because we don’t have all the samples for later-stage disease,” Ms. Quinn Young said in an interview. “And even with the clinical data, given the patient population, both [in terms of] demographics and the nature of the disease, the numbers of patients still living after multiple relapses is rather small.”

In an earlier effort to gather more data, the MMRF first turned to other organizations for help, but this approach fell short because of scarcity of data, and in some cases, unwillingness to share. Steven Labkoff, MD, chief data officer at the MMRF, described this experience in an interview.

NATIONAL HARBOR, MD – An armored chimeric antigen receptor (CAR) T-cell therapy has demonstrated efficacy in vitro and in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to findings presented at the annual meeting of the Society for Immunotherapy of Cancer.

Penn Medicine

ICTCAR014, a dominant negative PD-1 armored CAR T-cell therapy, proved more cytotoxic than traditional CAR T-cell therapy in vitro and produced responses in 12 of 13 NHL patients who received it.

Xiaobin Victor Lu, PhD, of Innovative Cellular Therapeutics, Shanghai, China, presented results with ICTCAR014 at the meeting.

Dr. Lu explained that ICTCAR014 consists of CD19-targeted CAR T cells genetically engineered to overexpress a PD-1 dominant negative protein with an altered intracellular signaling domain. The dominant negative protein can act as a “decoy receptor” to bind and block the PD-L1/2 inhibitory signal, thereby enhancing the efficacy of CAR T cells.

Innovative Cellular Therapeutics is developing ICTCAR014 because there is “some room to improve” with commercially available CAR T-cell products, Dr. Lu said. Specifically, tisagenlecleucel produced a 52% response rate in the JULIET trial (N Engl J Med. 2019;380:45-56), and axicabtagene ciloleucel produced an 82% response rate in the ZUMA-1 trial (N Engl J Med. 2017;377:2531-44).

There is also evidence to suggest that PD-1 blockade can modulate and “refuel” CAR T cells in relapsed/refractory NHL patients who fail or relapse after traditional anti-CD19 CAR T-cell therapy (Blood. 2017 Feb 23;129[8]:1039-41). This finding has prompted researchers to conduct trials of PD-1 inhibitors in combination with CAR T-cell therapies. But this combination approach may be expensive and cause more side effects than the armored CAR T-cell approach, Dr. Lu said.

In preclinical studies, Dr. Lu and colleagues found that ICTCAR014 was more effective than traditional anti-CD19 CAR T cells in killing Nalm6-PDL1 cells. In addition, the PD-1 dominant negative protein protected CAR T cells from exhaustion.

Dr. Lu also presented results in 13 NHL patients who have received ICTCAR014 in a phase 1 trial in China. Eleven patients had diffuse large B-cell lymphoma (DLBCL), and two had follicular lymphoma.

The objective response rate was 92.3% (12/13), which included five partial responses (38.5%) and seven complete responses (53.8%). Both follicular lymphoma patients and five DLBCL patients achieved a complete response. Five DLBCL patients achieved a partial response, and the remaining DLBCL patient did not respond.

Dr. Lu did not present safety data. However, he reported that there was no increased incidence of cytokine release syndrome or neurotoxicity in these patients, compared with patients receiving traditional CAR T-cell therapy.

Dr. Lu is employed by Innovative Cellular Therapeutics, which funded the research and is developing ICTCAR014.

[email protected]

SOURCE: Lu V et al. SITC 2019, Abstract O25.

NATIONAL HARBOR, MD – An armored chimeric antigen receptor (CAR) T-cell therapy has demonstrated efficacy in vitro and in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to findings presented at the annual meeting of the Society for Immunotherapy of Cancer.

Penn Medicine

ICTCAR014, a dominant negative PD-1 armored CAR T-cell therapy, proved more cytotoxic than traditional CAR T-cell therapy in vitro and produced responses in 12 of 13 NHL patients who received it.

Xiaobin Victor Lu, PhD, of Innovative Cellular Therapeutics, Shanghai, China, presented results with ICTCAR014 at the meeting.

Dr. Lu explained that ICTCAR014 consists of CD19-targeted CAR T cells genetically engineered to overexpress a PD-1 dominant negative protein with an altered intracellular signaling domain. The dominant negative protein can act as a “decoy receptor” to bind and block the PD-L1/2 inhibitory signal, thereby enhancing the efficacy of CAR T cells.

Innovative Cellular Therapeutics is developing ICTCAR014 because there is “some room to improve” with commercially available CAR T-cell products, Dr. Lu said. Specifically, tisagenlecleucel produced a 52% response rate in the JULIET trial (N Engl J Med. 2019;380:45-56), and axicabtagene ciloleucel produced an 82% response rate in the ZUMA-1 trial (N Engl J Med. 2017;377:2531-44).

There is also evidence to suggest that PD-1 blockade can modulate and “refuel” CAR T cells in relapsed/refractory NHL patients who fail or relapse after traditional anti-CD19 CAR T-cell therapy (Blood. 2017 Feb 23;129[8]:1039-41). This finding has prompted researchers to conduct trials of PD-1 inhibitors in combination with CAR T-cell therapies. But this combination approach may be expensive and cause more side effects than the armored CAR T-cell approach, Dr. Lu said.

In preclinical studies, Dr. Lu and colleagues found that ICTCAR014 was more effective than traditional anti-CD19 CAR T cells in killing Nalm6-PDL1 cells. In addition, the PD-1 dominant negative protein protected CAR T cells from exhaustion.

Dr. Lu also presented results in 13 NHL patients who have received ICTCAR014 in a phase 1 trial in China. Eleven patients had diffuse large B-cell lymphoma (DLBCL), and two had follicular lymphoma.

The objective response rate was 92.3% (12/13), which included five partial responses (38.5%) and seven complete responses (53.8%). Both follicular lymphoma patients and five DLBCL patients achieved a complete response. Five DLBCL patients achieved a partial response, and the remaining DLBCL patient did not respond.

Dr. Lu did not present safety data. However, he reported that there was no increased incidence of cytokine release syndrome or neurotoxicity in these patients, compared with patients receiving traditional CAR T-cell therapy.

Dr. Lu is employed by Innovative Cellular Therapeutics, which funded the research and is developing ICTCAR014.

[email protected]

SOURCE: Lu V et al. SITC 2019, Abstract O25.

NATIONAL HARBOR, MD – An armored chimeric antigen receptor (CAR) T-cell therapy has demonstrated efficacy in vitro and in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to findings presented at the annual meeting of the Society for Immunotherapy of Cancer.

Penn Medicine

ICTCAR014, a dominant negative PD-1 armored CAR T-cell therapy, proved more cytotoxic than traditional CAR T-cell therapy in vitro and produced responses in 12 of 13 NHL patients who received it.

Xiaobin Victor Lu, PhD, of Innovative Cellular Therapeutics, Shanghai, China, presented results with ICTCAR014 at the meeting.

Dr. Lu explained that ICTCAR014 consists of CD19-targeted CAR T cells genetically engineered to overexpress a PD-1 dominant negative protein with an altered intracellular signaling domain. The dominant negative protein can act as a “decoy receptor” to bind and block the PD-L1/2 inhibitory signal, thereby enhancing the efficacy of CAR T cells.

Innovative Cellular Therapeutics is developing ICTCAR014 because there is “some room to improve” with commercially available CAR T-cell products, Dr. Lu said. Specifically, tisagenlecleucel produced a 52% response rate in the JULIET trial (N Engl J Med. 2019;380:45-56), and axicabtagene ciloleucel produced an 82% response rate in the ZUMA-1 trial (N Engl J Med. 2017;377:2531-44).

There is also evidence to suggest that PD-1 blockade can modulate and “refuel” CAR T cells in relapsed/refractory NHL patients who fail or relapse after traditional anti-CD19 CAR T-cell therapy (Blood. 2017 Feb 23;129[8]:1039-41). This finding has prompted researchers to conduct trials of PD-1 inhibitors in combination with CAR T-cell therapies. But this combination approach may be expensive and cause more side effects than the armored CAR T-cell approach, Dr. Lu said.

In preclinical studies, Dr. Lu and colleagues found that ICTCAR014 was more effective than traditional anti-CD19 CAR T cells in killing Nalm6-PDL1 cells. In addition, the PD-1 dominant negative protein protected CAR T cells from exhaustion.

Dr. Lu also presented results in 13 NHL patients who have received ICTCAR014 in a phase 1 trial in China. Eleven patients had diffuse large B-cell lymphoma (DLBCL), and two had follicular lymphoma.

The objective response rate was 92.3% (12/13), which included five partial responses (38.5%) and seven complete responses (53.8%). Both follicular lymphoma patients and five DLBCL patients achieved a complete response. Five DLBCL patients achieved a partial response, and the remaining DLBCL patient did not respond.

Dr. Lu did not present safety data. However, he reported that there was no increased incidence of cytokine release syndrome or neurotoxicity in these patients, compared with patients receiving traditional CAR T-cell therapy.

Dr. Lu is employed by Innovative Cellular Therapeutics, which funded the research and is developing ICTCAR014.

[email protected]

SOURCE: Lu V et al. SITC 2019, Abstract O25.

The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.

By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.

“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.

The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.

In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.

The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.

Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.

With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.

The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.

MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.

In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.

The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.

SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.

The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.

By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.

“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.

The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.

In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.

The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.

Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.

With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.

The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.

MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.

In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.

The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.

SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.

The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.

By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.

“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.

The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.

In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.

The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.

Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.

With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.

The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.

MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.

In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.

The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.

SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.

Adding levofloxacin to antimyeloma therapy improved survival and reduced infections in patients with newly diagnosed myeloma, findings from a phase 3 trial suggest.

Wikimedia Commons/KGH/Creative Commons License

The advantages of levofloxacin prophylaxis appear to offset the potential risks in patients with newly diagnosed disease, explained Mark T. Drayson, MBChB, PhD, of the University of Birmingham (England) and colleagues. The study was published in the Lancet Oncology.

The randomized, placebo-controlled, phase 3 TEAMM study enrolled 977 patients with newly diagnosed myeloma. The effects of antimicrobial prophylaxis on infection risk and infection-related mortality were evaluated across 93 hospitals throughout the United Kingdom.

Study patients were randomly assigned to receive 500 mg of oral levofloxacin once daily or placebo for a total of 12 weeks. If applicable, dose adjustments were made based on estimated glomerular filtration rate.

At baseline, the team collected stool samples and nasal swabs, and follow-up assessment occurred every 4 weeks for up to 1 year. The primary endpoint was time to death (all causes) or first febrile event from the start of prophylactic therapy to 12 weeks.

After a median follow-up of 12 months, first febrile episodes or deaths were significantly lower for patients in the levofloxacin arm (19%), compared with the placebo arm (27%) for a hazard ratio for time to first event of 0.66 (95% confidence interval, 0.51-0.86; P = .0018).

With respect to safety, the rates of serious adverse events were similar between the study arms, with the exception of tendinitis in the levofloxacin group (1%). Among all patients, a total of 597 serious toxicities were observed from baseline to 16 weeks (52% in the levofloxacin arm vs. 48% in the placebo arm).

“To our knowledge, this is the first time that the use of prophylactic antibiotics has shown a survival benefit in patients with newly diagnosed myeloma,” the researchers reported.

One key limitation of the study was the younger patient population relative to the general population. As a result, differences in survival estimates could exist between the trial and real-world populations, they noted.

“Patients with newly diagnosed myeloma could benefit from levofloxacin prophylaxis, although local antibiotic resistance proportions must be considered,” the researchers cautioned.

The study was funded by the National Institute for Health Research in the United Kingdom. The authors reported financial affiliations with Actelion, Astellas, Celgene, Gilead, Janssen, Pfizer, Takeda, and other companies.

SOURCE: Drayson MT et al. Lancet Oncol. 2019 Oct 23. doi: 10.1016/S1470-2045(19)30506-6.

Adding levofloxacin to antimyeloma therapy improved survival and reduced infections in patients with newly diagnosed myeloma, findings from a phase 3 trial suggest.

Wikimedia Commons/KGH/Creative Commons License

The advantages of levofloxacin prophylaxis appear to offset the potential risks in patients with newly diagnosed disease, explained Mark T. Drayson, MBChB, PhD, of the University of Birmingham (England) and colleagues. The study was published in the Lancet Oncology.

The randomized, placebo-controlled, phase 3 TEAMM study enrolled 977 patients with newly diagnosed myeloma. The effects of antimicrobial prophylaxis on infection risk and infection-related mortality were evaluated across 93 hospitals throughout the United Kingdom.

Study patients were randomly assigned to receive 500 mg of oral levofloxacin once daily or placebo for a total of 12 weeks. If applicable, dose adjustments were made based on estimated glomerular filtration rate.

At baseline, the team collected stool samples and nasal swabs, and follow-up assessment occurred every 4 weeks for up to 1 year. The primary endpoint was time to death (all causes) or first febrile event from the start of prophylactic therapy to 12 weeks.

After a median follow-up of 12 months, first febrile episodes or deaths were significantly lower for patients in the levofloxacin arm (19%), compared with the placebo arm (27%) for a hazard ratio for time to first event of 0.66 (95% confidence interval, 0.51-0.86; P = .0018).

With respect to safety, the rates of serious adverse events were similar between the study arms, with the exception of tendinitis in the levofloxacin group (1%). Among all patients, a total of 597 serious toxicities were observed from baseline to 16 weeks (52% in the levofloxacin arm vs. 48% in the placebo arm).

“To our knowledge, this is the first time that the use of prophylactic antibiotics has shown a survival benefit in patients with newly diagnosed myeloma,” the researchers reported.

One key limitation of the study was the younger patient population relative to the general population. As a result, differences in survival estimates could exist between the trial and real-world populations, they noted.

“Patients with newly diagnosed myeloma could benefit from levofloxacin prophylaxis, although local antibiotic resistance proportions must be considered,” the researchers cautioned.

The study was funded by the National Institute for Health Research in the United Kingdom. The authors reported financial affiliations with Actelion, Astellas, Celgene, Gilead, Janssen, Pfizer, Takeda, and other companies.

SOURCE: Drayson MT et al. Lancet Oncol. 2019 Oct 23. doi: 10.1016/S1470-2045(19)30506-6.

Adding levofloxacin to antimyeloma therapy improved survival and reduced infections in patients with newly diagnosed myeloma, findings from a phase 3 trial suggest.

Wikimedia Commons/KGH/Creative Commons License

The advantages of levofloxacin prophylaxis appear to offset the potential risks in patients with newly diagnosed disease, explained Mark T. Drayson, MBChB, PhD, of the University of Birmingham (England) and colleagues. The study was published in the Lancet Oncology.

The randomized, placebo-controlled, phase 3 TEAMM study enrolled 977 patients with newly diagnosed myeloma. The effects of antimicrobial prophylaxis on infection risk and infection-related mortality were evaluated across 93 hospitals throughout the United Kingdom.

Study patients were randomly assigned to receive 500 mg of oral levofloxacin once daily or placebo for a total of 12 weeks. If applicable, dose adjustments were made based on estimated glomerular filtration rate.

At baseline, the team collected stool samples and nasal swabs, and follow-up assessment occurred every 4 weeks for up to 1 year. The primary endpoint was time to death (all causes) or first febrile event from the start of prophylactic therapy to 12 weeks.

After a median follow-up of 12 months, first febrile episodes or deaths were significantly lower for patients in the levofloxacin arm (19%), compared with the placebo arm (27%) for a hazard ratio for time to first event of 0.66 (95% confidence interval, 0.51-0.86; P = .0018).

With respect to safety, the rates of serious adverse events were similar between the study arms, with the exception of tendinitis in the levofloxacin group (1%). Among all patients, a total of 597 serious toxicities were observed from baseline to 16 weeks (52% in the levofloxacin arm vs. 48% in the placebo arm).

“To our knowledge, this is the first time that the use of prophylactic antibiotics has shown a survival benefit in patients with newly diagnosed myeloma,” the researchers reported.

One key limitation of the study was the younger patient population relative to the general population. As a result, differences in survival estimates could exist between the trial and real-world populations, they noted.

“Patients with newly diagnosed myeloma could benefit from levofloxacin prophylaxis, although local antibiotic resistance proportions must be considered,” the researchers cautioned.

The study was funded by the National Institute for Health Research in the United Kingdom. The authors reported financial affiliations with Actelion, Astellas, Celgene, Gilead, Janssen, Pfizer, Takeda, and other companies.

SOURCE: Drayson MT et al. Lancet Oncol. 2019 Oct 23. doi: 10.1016/S1470-2045(19)30506-6.

EDINBURGH – Impaired renal function may indicate excess risk of tumor lysis syndrome (TLS) in venetoclax-treated chronic lymphocytic leukemia (CLL) patients and should be considered when assessing TLS risk, according to findings from a retrospective cohort study.

Complex karyotype may also affect TLS risk, Anthony Mato, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Of 339 CLL patients who were treated with venetoclax, 38%, 34%, and 28% were considered to have low, medium, or high risk for TLS, respectively, according to the standard definition based on absolute lymphocyte count as a measure of tumor burden and/or lymph node size.

TLS occurred in 35 patients (10%), including 26 cases of laboratory-confirmed TLS and 9 clinical TLS cases; 1 patient required dialysis and 1 death occurred, which was attributable to the TLS, Dr. Mato of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported in a poster at the workshop.

Univariate analysis was performed to “understand baseline factors associated with TLS development during dose escalation,” and it examined sex, creatinine clearance (CrCl), complex karyotype, immunoglobulin heavy chain variable mutation status, prior ibrutinib exposure, venetoclax monotherapy vs. combination therapy, and TLS risk group. The investigators observed no significant difference between the low- and medium-risk patients, therefore those two groups were combined and compared with the high-risk patients.

The univariate analysis showed significant associations between TLS and CrCl (odds ratio, 2.9 for 80 mL/min or less vs. greater than 80 mL/min), complex karyotype (OR, 2.2), and low/medium vs. high TLS risk based on the standard definition (OR, 2.56).

A multivariable analysis of the predictors identified as significant in the univariate analyses showed that standard TLS risk group and CrCl remained independent predictors of TLS.

“Although the odds ratio for complex karyotype suggested potential clinical significance, this did not meet the threshold for statistical significance and was not included in the final model,” they wrote.

The area under the receiver operating characteristic curve for a model including TLS risk group and CrCl was 74.6%, compared with 65% for the area under the ROC curve using the standard tumor burden/lymph node size approach for defining TLS risk, which is described in the venetoclax package insert.

Patients included in the study had a median age of 67 years at venetoclax initiation, 69% were men, 85% were white, and 13% were treated on a clinical trial. Complex karyotype was present in 39%, del(17p) in 43%, and 84% had immunoglobulin heavy chain variable–unmutated disease.

Most patients received venetoclax monotherapy (79%), had relapsed/refractory disease (94%), and had previously received ibrutinib (78%). The median number of prior therapies was 3, but the number ranged from 0-15, the investigators noted.

The findings of this study suggest that, in addition to defining risk based on absolute lymphocyte count and lymph node size, patients with CrCl less than 80 mL/min – indicating impaired renal function – have excess risk of TLS.

Although complex karyotype did not reach statistical significance as an independent predictor of TLS, the findings in this study suggest it “may impact TLS risk and is worthy of further study in larger samples,” they said, concluding that consideration of baseline renal function, and possibly karyotype, could “further guide practitioners in their approach to prophylaxis and patient counseling, allowing for improved safety in the use of this effective agent in CLL.”

Additional planned analyses will focus on TLS risk score development and further refinement of TLS risk stratification, they noted.

Dr. Mato has received grant support, consulting fees, and/or fees for serving on a data and safety monitoring board or advisory board from AbbVie, AstraZeneca, Celgene, Janssen, TG Therapeutics, Pharmacyclics, Loxo, Sunesis, prIME Oncology, Pfizer, Johnson & Johnson, and Regeneron.

[email protected]

EDINBURGH – Impaired renal function may indicate excess risk of tumor lysis syndrome (TLS) in venetoclax-treated chronic lymphocytic leukemia (CLL) patients and should be considered when assessing TLS risk, according to findings from a retrospective cohort study.

Complex karyotype may also affect TLS risk, Anthony Mato, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Of 339 CLL patients who were treated with venetoclax, 38%, 34%, and 28% were considered to have low, medium, or high risk for TLS, respectively, according to the standard definition based on absolute lymphocyte count as a measure of tumor burden and/or lymph node size.

TLS occurred in 35 patients (10%), including 26 cases of laboratory-confirmed TLS and 9 clinical TLS cases; 1 patient required dialysis and 1 death occurred, which was attributable to the TLS, Dr. Mato of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported in a poster at the workshop.

Univariate analysis was performed to “understand baseline factors associated with TLS development during dose escalation,” and it examined sex, creatinine clearance (CrCl), complex karyotype, immunoglobulin heavy chain variable mutation status, prior ibrutinib exposure, venetoclax monotherapy vs. combination therapy, and TLS risk group. The investigators observed no significant difference between the low- and medium-risk patients, therefore those two groups were combined and compared with the high-risk patients.

The univariate analysis showed significant associations between TLS and CrCl (odds ratio, 2.9 for 80 mL/min or less vs. greater than 80 mL/min), complex karyotype (OR, 2.2), and low/medium vs. high TLS risk based on the standard definition (OR, 2.56).

A multivariable analysis of the predictors identified as significant in the univariate analyses showed that standard TLS risk group and CrCl remained independent predictors of TLS.

“Although the odds ratio for complex karyotype suggested potential clinical significance, this did not meet the threshold for statistical significance and was not included in the final model,” they wrote.

The area under the receiver operating characteristic curve for a model including TLS risk group and CrCl was 74.6%, compared with 65% for the area under the ROC curve using the standard tumor burden/lymph node size approach for defining TLS risk, which is described in the venetoclax package insert.

Patients included in the study had a median age of 67 years at venetoclax initiation, 69% were men, 85% were white, and 13% were treated on a clinical trial. Complex karyotype was present in 39%, del(17p) in 43%, and 84% had immunoglobulin heavy chain variable–unmutated disease.

Most patients received venetoclax monotherapy (79%), had relapsed/refractory disease (94%), and had previously received ibrutinib (78%). The median number of prior therapies was 3, but the number ranged from 0-15, the investigators noted.

The findings of this study suggest that, in addition to defining risk based on absolute lymphocyte count and lymph node size, patients with CrCl less than 80 mL/min – indicating impaired renal function – have excess risk of TLS.

Although complex karyotype did not reach statistical significance as an independent predictor of TLS, the findings in this study suggest it “may impact TLS risk and is worthy of further study in larger samples,” they said, concluding that consideration of baseline renal function, and possibly karyotype, could “further guide practitioners in their approach to prophylaxis and patient counseling, allowing for improved safety in the use of this effective agent in CLL.”

Additional planned analyses will focus on TLS risk score development and further refinement of TLS risk stratification, they noted.

Dr. Mato has received grant support, consulting fees, and/or fees for serving on a data and safety monitoring board or advisory board from AbbVie, AstraZeneca, Celgene, Janssen, TG Therapeutics, Pharmacyclics, Loxo, Sunesis, prIME Oncology, Pfizer, Johnson & Johnson, and Regeneron.

[email protected]

EDINBURGH – Impaired renal function may indicate excess risk of tumor lysis syndrome (TLS) in venetoclax-treated chronic lymphocytic leukemia (CLL) patients and should be considered when assessing TLS risk, according to findings from a retrospective cohort study.

Complex karyotype may also affect TLS risk, Anthony Mato, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Of 339 CLL patients who were treated with venetoclax, 38%, 34%, and 28% were considered to have low, medium, or high risk for TLS, respectively, according to the standard definition based on absolute lymphocyte count as a measure of tumor burden and/or lymph node size.

TLS occurred in 35 patients (10%), including 26 cases of laboratory-confirmed TLS and 9 clinical TLS cases; 1 patient required dialysis and 1 death occurred, which was attributable to the TLS, Dr. Mato of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported in a poster at the workshop.

Univariate analysis was performed to “understand baseline factors associated with TLS development during dose escalation,” and it examined sex, creatinine clearance (CrCl), complex karyotype, immunoglobulin heavy chain variable mutation status, prior ibrutinib exposure, venetoclax monotherapy vs. combination therapy, and TLS risk group. The investigators observed no significant difference between the low- and medium-risk patients, therefore those two groups were combined and compared with the high-risk patients.

The univariate analysis showed significant associations between TLS and CrCl (odds ratio, 2.9 for 80 mL/min or less vs. greater than 80 mL/min), complex karyotype (OR, 2.2), and low/medium vs. high TLS risk based on the standard definition (OR, 2.56).

A multivariable analysis of the predictors identified as significant in the univariate analyses showed that standard TLS risk group and CrCl remained independent predictors of TLS.

“Although the odds ratio for complex karyotype suggested potential clinical significance, this did not meet the threshold for statistical significance and was not included in the final model,” they wrote.

The area under the receiver operating characteristic curve for a model including TLS risk group and CrCl was 74.6%, compared with 65% for the area under the ROC curve using the standard tumor burden/lymph node size approach for defining TLS risk, which is described in the venetoclax package insert.

Patients included in the study had a median age of 67 years at venetoclax initiation, 69% were men, 85% were white, and 13% were treated on a clinical trial. Complex karyotype was present in 39%, del(17p) in 43%, and 84% had immunoglobulin heavy chain variable–unmutated disease.

Most patients received venetoclax monotherapy (79%), had relapsed/refractory disease (94%), and had previously received ibrutinib (78%). The median number of prior therapies was 3, but the number ranged from 0-15, the investigators noted.

The findings of this study suggest that, in addition to defining risk based on absolute lymphocyte count and lymph node size, patients with CrCl less than 80 mL/min – indicating impaired renal function – have excess risk of TLS.

Although complex karyotype did not reach statistical significance as an independent predictor of TLS, the findings in this study suggest it “may impact TLS risk and is worthy of further study in larger samples,” they said, concluding that consideration of baseline renal function, and possibly karyotype, could “further guide practitioners in their approach to prophylaxis and patient counseling, allowing for improved safety in the use of this effective agent in CLL.”

Additional planned analyses will focus on TLS risk score development and further refinement of TLS risk stratification, they noted.

Dr. Mato has received grant support, consulting fees, and/or fees for serving on a data and safety monitoring board or advisory board from AbbVie, AstraZeneca, Celgene, Janssen, TG Therapeutics, Pharmacyclics, Loxo, Sunesis, prIME Oncology, Pfizer, Johnson & Johnson, and Regeneron.

[email protected]

Breast implants sold in the United States may soon require a boxed warning in their label, along with other label changes proposed by the Food and Drug Administration aimed at better informing prospective patients and clinicians of the potential risks from breast implants.

Mitchel L. Zoler/MDedge News

Other elements of the proposed labeling changes include creation of a patient-decision checklist, new recommendations for follow-up imaging to monitor for implant rupture, inclusion of detailed and understandable information about materials in the device, and provision of a device card to each patient with details on the specific implant they received.

These labeling changes all stemmed from a breast implant hearing held by the agency’s General and Plastic Surgery Devices Panel in March 2019, according to the draft guidance document officially released by the FDA on Oct. 24.

The proposed labeling changes were generally welcomed by patient advocates and by clinicians as a reasonable response to the concerns discussed at the March hearing. In an earlier move to address issues brought up at the hearing, the FDA in July arranged for a recall for certain Allergan models of textured breast implants because of their link with the development of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL).

The boxed warning proposed by the FDA would highlight four specific facts that patients, physicians, and surgeons should know about breast implants: They are not considered lifetime devices, the chance of developing complications from implants increases over time, some complications require additional surgery, and placement of breast implants has been associated with development of BIA-ALCL and may also be associated with certain systemic symptoms.

The FDA also proposed four other notable labeling changes:

• Creation of a patient-decision checklist to better systematize the informed consent process and make sure that certain aspects of breast implant placement are clearly brought to patients’ attention. The FDA proposed that patients sign their checklist attesting to having read and understood the information and that patients receive a take-home copy for their future reference. Proposed elements of the checklist include situations to not use breast implants; considerations for successful implant recipients; the risks of breast implant surgery; the importance of appropriate physician education, training, and experience; the risk for developing BIA-ALCL or systemic symptoms; and discussion of options other than breast implants.
• A new scheme for systematically and serially using imaging to screen for implant rupture that designates for the first time that ultrasound is an acceptable alternative to MRI and relies on a schedule by which either method initially screens the implant 5-6 years post operatively and then every 2 years thereafter.
• Detailed and understandable information about each material component of the implant with further information on possible adverse health effects of these compounds.
• A device card that patients should receive after their surgery with the implant’s name, serial number, and other identifiers; the boxed warning information; and a web link for accessing more up-to-date information.

The patient group Breast Implant Victim Advocacy praised the draft guidance. “The March Advisory Committee meeting seems to have prompted a shift by the FDA, surgeons, and industry,” said Jamee Cook, cofounder of the group. “We are definitely seeing a change in patient engagement. The FDA has been cooperating with patients and listening to our concerns. We still have a long way to go in raising public awareness of breast implant issues, but progress over the past 1-2 years has been amazing.”

Diana Zuckerman, PhD, president of the National Center for Health Research in Washington, gave the draft guidance a mixed review. “The FDA’s draft includes the types of information that we had proposed to the FDA in recent months in our work with patient advocates and plastic surgeons,” she said. “However, it is not as informative as it should be in describing well-designed studies indicating a risk of systemic illnesses. Patients deserve to make better-informed decisions in the future than most women considering breast implants have been able to make” in the past.

Patricia McGuire, MD, a St. Louis plastic surgeon who specializes in breast surgery and has studied breast implant illness, declared the guidance to be “reasonable.”

“I think the changes address the concerns expressed by patients during the [March] hearing; I agree with everything the FDA proposed in the guidance document,” Dr. McGuire said. “The boxed warning is reasonable and needs to be part of the informed consent process. I also agree with the changes in screening implants postoperatively. Most patients do not get MRI examinations. High-resolution ultrasound is more convenient and cost effective.”

The boxed warning was rated as “reasonably strong” and “the most serious step the FDA can take short of taking a device off the market,” but in the case of breast implants, a wider recall of textured implants than what the FDA arranged last July would be even more appropriate, commented Sidney M. Wolfe, MD, founder and senior adviser to Public Citizen. He also faulted the agency for not taking quicker action in mandating inclusion of the proposed boxed warning.

Issuing the labeling changes as draft guidance “is a ministep forward,” but also a process that “guarantees delay” and “creeps along at a dangerously slow pace,” Dr. Wolfe said. “The FDA is delaying what should be inevitable. The agency could put the boxed warning in place right now if they had the guts to do it.”

Dr. McGuire has been a consultant to Allergan, Establishment Labs, and Hans Biomed. Ms. Cook, Dr. Zuckerman, and Dr. Wolfe reported having no commercial disclosures.

[email protected]

Breast implants sold in the United States may soon require a boxed warning in their label, along with other label changes proposed by the Food and Drug Administration aimed at better informing prospective patients and clinicians of the potential risks from breast implants.

Mitchel L. Zoler/MDedge News

Other elements of the proposed labeling changes include creation of a patient-decision checklist, new recommendations for follow-up imaging to monitor for implant rupture, inclusion of detailed and understandable information about materials in the device, and provision of a device card to each patient with details on the specific implant they received.

These labeling changes all stemmed from a breast implant hearing held by the agency’s General and Plastic Surgery Devices Panel in March 2019, according to the draft guidance document officially released by the FDA on Oct. 24.

The proposed labeling changes were generally welcomed by patient advocates and by clinicians as a reasonable response to the concerns discussed at the March hearing. In an earlier move to address issues brought up at the hearing, the FDA in July arranged for a recall for certain Allergan models of textured breast implants because of their link with the development of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL).

The boxed warning proposed by the FDA would highlight four specific facts that patients, physicians, and surgeons should know about breast implants: They are not considered lifetime devices, the chance of developing complications from implants increases over time, some complications require additional surgery, and placement of breast implants has been associated with development of BIA-ALCL and may also be associated with certain systemic symptoms.

The FDA also proposed four other notable labeling changes:

• Creation of a patient-decision checklist to better systematize the informed consent process and make sure that certain aspects of breast implant placement are clearly brought to patients’ attention. The FDA proposed that patients sign their checklist attesting to having read and understood the information and that patients receive a take-home copy for their future reference. Proposed elements of the checklist include situations to not use breast implants; considerations for successful implant recipients; the risks of breast implant surgery; the importance of appropriate physician education, training, and experience; the risk for developing BIA-ALCL or systemic symptoms; and discussion of options other than breast implants.
• A new scheme for systematically and serially using imaging to screen for implant rupture that designates for the first time that ultrasound is an acceptable alternative to MRI and relies on a schedule by which either method initially screens the implant 5-6 years post operatively and then every 2 years thereafter.
• Detailed and understandable information about each material component of the implant with further information on possible adverse health effects of these compounds.
• A device card that patients should receive after their surgery with the implant’s name, serial number, and other identifiers; the boxed warning information; and a web link for accessing more up-to-date information.

The patient group Breast Implant Victim Advocacy praised the draft guidance. “The March Advisory Committee meeting seems to have prompted a shift by the FDA, surgeons, and industry,” said Jamee Cook, cofounder of the group. “We are definitely seeing a change in patient engagement. The FDA has been cooperating with patients and listening to our concerns. We still have a long way to go in raising public awareness of breast implant issues, but progress over the past 1-2 years has been amazing.”

Diana Zuckerman, PhD, president of the National Center for Health Research in Washington, gave the draft guidance a mixed review. “The FDA’s draft includes the types of information that we had proposed to the FDA in recent months in our work with patient advocates and plastic surgeons,” she said. “However, it is not as informative as it should be in describing well-designed studies indicating a risk of systemic illnesses. Patients deserve to make better-informed decisions in the future than most women considering breast implants have been able to make” in the past.

Patricia McGuire, MD, a St. Louis plastic surgeon who specializes in breast surgery and has studied breast implant illness, declared the guidance to be “reasonable.”

“I think the changes address the concerns expressed by patients during the [March] hearing; I agree with everything the FDA proposed in the guidance document,” Dr. McGuire said. “The boxed warning is reasonable and needs to be part of the informed consent process. I also agree with the changes in screening implants postoperatively. Most patients do not get MRI examinations. High-resolution ultrasound is more convenient and cost effective.”

The boxed warning was rated as “reasonably strong” and “the most serious step the FDA can take short of taking a device off the market,” but in the case of breast implants, a wider recall of textured implants than what the FDA arranged last July would be even more appropriate, commented Sidney M. Wolfe, MD, founder and senior adviser to Public Citizen. He also faulted the agency for not taking quicker action in mandating inclusion of the proposed boxed warning.

Issuing the labeling changes as draft guidance “is a ministep forward,” but also a process that “guarantees delay” and “creeps along at a dangerously slow pace,” Dr. Wolfe said. “The FDA is delaying what should be inevitable. The agency could put the boxed warning in place right now if they had the guts to do it.”

Dr. McGuire has been a consultant to Allergan, Establishment Labs, and Hans Biomed. Ms. Cook, Dr. Zuckerman, and Dr. Wolfe reported having no commercial disclosures.

[email protected]

Breast implants sold in the United States may soon require a boxed warning in their label, along with other label changes proposed by the Food and Drug Administration aimed at better informing prospective patients and clinicians of the potential risks from breast implants.

Mitchel L. Zoler/MDedge News

Other elements of the proposed labeling changes include creation of a patient-decision checklist, new recommendations for follow-up imaging to monitor for implant rupture, inclusion of detailed and understandable information about materials in the device, and provision of a device card to each patient with details on the specific implant they received.

These labeling changes all stemmed from a breast implant hearing held by the agency’s General and Plastic Surgery Devices Panel in March 2019, according to the draft guidance document officially released by the FDA on Oct. 24.

The proposed labeling changes were generally welcomed by patient advocates and by clinicians as a reasonable response to the concerns discussed at the March hearing. In an earlier move to address issues brought up at the hearing, the FDA in July arranged for a recall for certain Allergan models of textured breast implants because of their link with the development of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL).

The boxed warning proposed by the FDA would highlight four specific facts that patients, physicians, and surgeons should know about breast implants: They are not considered lifetime devices, the chance of developing complications from implants increases over time, some complications require additional surgery, and placement of breast implants has been associated with development of BIA-ALCL and may also be associated with certain systemic symptoms.

The FDA also proposed four other notable labeling changes:

• Creation of a patient-decision checklist to better systematize the informed consent process and make sure that certain aspects of breast implant placement are clearly brought to patients’ attention. The FDA proposed that patients sign their checklist attesting to having read and understood the information and that patients receive a take-home copy for their future reference. Proposed elements of the checklist include situations to not use breast implants; considerations for successful implant recipients; the risks of breast implant surgery; the importance of appropriate physician education, training, and experience; the risk for developing BIA-ALCL or systemic symptoms; and discussion of options other than breast implants.
• A new scheme for systematically and serially using imaging to screen for implant rupture that designates for the first time that ultrasound is an acceptable alternative to MRI and relies on a schedule by which either method initially screens the implant 5-6 years post operatively and then every 2 years thereafter.
• Detailed and understandable information about each material component of the implant with further information on possible adverse health effects of these compounds.
• A device card that patients should receive after their surgery with the implant’s name, serial number, and other identifiers; the boxed warning information; and a web link for accessing more up-to-date information.

The patient group Breast Implant Victim Advocacy praised the draft guidance. “The March Advisory Committee meeting seems to have prompted a shift by the FDA, surgeons, and industry,” said Jamee Cook, cofounder of the group. “We are definitely seeing a change in patient engagement. The FDA has been cooperating with patients and listening to our concerns. We still have a long way to go in raising public awareness of breast implant issues, but progress over the past 1-2 years has been amazing.”

Diana Zuckerman, PhD, president of the National Center for Health Research in Washington, gave the draft guidance a mixed review. “The FDA’s draft includes the types of information that we had proposed to the FDA in recent months in our work with patient advocates and plastic surgeons,” she said. “However, it is not as informative as it should be in describing well-designed studies indicating a risk of systemic illnesses. Patients deserve to make better-informed decisions in the future than most women considering breast implants have been able to make” in the past.

Patricia McGuire, MD, a St. Louis plastic surgeon who specializes in breast surgery and has studied breast implant illness, declared the guidance to be “reasonable.”

“I think the changes address the concerns expressed by patients during the [March] hearing; I agree with everything the FDA proposed in the guidance document,” Dr. McGuire said. “The boxed warning is reasonable and needs to be part of the informed consent process. I also agree with the changes in screening implants postoperatively. Most patients do not get MRI examinations. High-resolution ultrasound is more convenient and cost effective.”

The boxed warning was rated as “reasonably strong” and “the most serious step the FDA can take short of taking a device off the market,” but in the case of breast implants, a wider recall of textured implants than what the FDA arranged last July would be even more appropriate, commented Sidney M. Wolfe, MD, founder and senior adviser to Public Citizen. He also faulted the agency for not taking quicker action in mandating inclusion of the proposed boxed warning.

Issuing the labeling changes as draft guidance “is a ministep forward,” but also a process that “guarantees delay” and “creeps along at a dangerously slow pace,” Dr. Wolfe said. “The FDA is delaying what should be inevitable. The agency could put the boxed warning in place right now if they had the guts to do it.”

Dr. McGuire has been a consultant to Allergan, Establishment Labs, and Hans Biomed. Ms. Cook, Dr. Zuckerman, and Dr. Wolfe reported having no commercial disclosures.

[email protected]

Black race, polypharmacy, and increasing age were associated with poor adherence to lenalidomide in older patients with newly-diagnosed multiple myeloma, according to an analysis of Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data.

©bbbrrn/Thinkstockphotos.com

The objective of the study was to examine factors affecting adherence in older adults who received lenalidomide.

Of 793 patients diagnosed and treated between 2007 and 2014, 302 (38%) had poor adherence to lenalidomide, reported Hira Mian, MD, of McMaster University, Hamilton, Ont., and colleagues. The findings were published in Clinical Lymphoma, Myeloma & Leukemia.

The researchers studied patients 65 years and older who had received at least two lenalidomide prescriptions in the first year following diagnosis. Only patients who filled a prescription for lenalidomide within 60 days of a myeloma diagnosis were included.

The median age of the patients was 73 years; 43% were aged 75 years or older. Most of the patients included in the analysis were white.

The medication possession ratio, defined as the “ratio of the number of days the patient had pills in their possession to the number of days in the observation period,” was used to evaluate adherence to therapy. A ratio of less than 90% was deemed poor adherence by the researchers.

After analysis, the researchers found that black race (adjusted odds ratio, 1.72; P = .022), polypharmacy (aOR, 1.04 per drug; P = .008), and increasing age (aOR, 1.03 per year; P = .024) were all significantly associated with poor adherence to lenalidomide.

The mean medication possession ratio among study patients was 89.5%. Overall, 38% of patients in the study had poor adherence to lenalidomide, while just 7% of patients in the study had a medication possession ratio of 100%, indicating “perfect adherence.”

There was a trend toward inferior overall survival among patients with poor adherence to lenalidomide, but it was not statistically significant (hazard ratio 1.10, 95% confidence interval, 0.88-1.38).

“Our study emphasizes the need for both better clinical monitoring of adherence and for future prospective studies in accurately understanding the rates and predictors of adherence while simultaneously developing strategies for improving adherence for patients that are at high risk of nonadherence,” the researchers wrote.

The National Institutes of Health funded the study. No conflicts of interest were reported.

SOURCE: Mian H et al. Clin Lymphoma Myeloma Leuk. 2019 Oct 9. doi: 10.1016/j.clml.2019.09.618.

Black race, polypharmacy, and increasing age were associated with poor adherence to lenalidomide in older patients with newly-diagnosed multiple myeloma, according to an analysis of Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data.

©bbbrrn/Thinkstockphotos.com

The objective of the study was to examine factors affecting adherence in older adults who received lenalidomide.

Of 793 patients diagnosed and treated between 2007 and 2014, 302 (38%) had poor adherence to lenalidomide, reported Hira Mian, MD, of McMaster University, Hamilton, Ont., and colleagues. The findings were published in Clinical Lymphoma, Myeloma & Leukemia.

The researchers studied patients 65 years and older who had received at least two lenalidomide prescriptions in the first year following diagnosis. Only patients who filled a prescription for lenalidomide within 60 days of a myeloma diagnosis were included.

The median age of the patients was 73 years; 43% were aged 75 years or older. Most of the patients included in the analysis were white.

The medication possession ratio, defined as the “ratio of the number of days the patient had pills in their possession to the number of days in the observation period,” was used to evaluate adherence to therapy. A ratio of less than 90% was deemed poor adherence by the researchers.

After analysis, the researchers found that black race (adjusted odds ratio, 1.72; P = .022), polypharmacy (aOR, 1.04 per drug; P = .008), and increasing age (aOR, 1.03 per year; P = .024) were all significantly associated with poor adherence to lenalidomide.

The mean medication possession ratio among study patients was 89.5%. Overall, 38% of patients in the study had poor adherence to lenalidomide, while just 7% of patients in the study had a medication possession ratio of 100%, indicating “perfect adherence.”

There was a trend toward inferior overall survival among patients with poor adherence to lenalidomide, but it was not statistically significant (hazard ratio 1.10, 95% confidence interval, 0.88-1.38).

“Our study emphasizes the need for both better clinical monitoring of adherence and for future prospective studies in accurately understanding the rates and predictors of adherence while simultaneously developing strategies for improving adherence for patients that are at high risk of nonadherence,” the researchers wrote.

The National Institutes of Health funded the study. No conflicts of interest were reported.

SOURCE: Mian H et al. Clin Lymphoma Myeloma Leuk. 2019 Oct 9. doi: 10.1016/j.clml.2019.09.618.

Black race, polypharmacy, and increasing age were associated with poor adherence to lenalidomide in older patients with newly-diagnosed multiple myeloma, according to an analysis of Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data.

©bbbrrn/Thinkstockphotos.com

The objective of the study was to examine factors affecting adherence in older adults who received lenalidomide.

Of 793 patients diagnosed and treated between 2007 and 2014, 302 (38%) had poor adherence to lenalidomide, reported Hira Mian, MD, of McMaster University, Hamilton, Ont., and colleagues. The findings were published in Clinical Lymphoma, Myeloma & Leukemia.

The researchers studied patients 65 years and older who had received at least two lenalidomide prescriptions in the first year following diagnosis. Only patients who filled a prescription for lenalidomide within 60 days of a myeloma diagnosis were included.

The median age of the patients was 73 years; 43% were aged 75 years or older. Most of the patients included in the analysis were white.

The medication possession ratio, defined as the “ratio of the number of days the patient had pills in their possession to the number of days in the observation period,” was used to evaluate adherence to therapy. A ratio of less than 90% was deemed poor adherence by the researchers.

After analysis, the researchers found that black race (adjusted odds ratio, 1.72; P = .022), polypharmacy (aOR, 1.04 per drug; P = .008), and increasing age (aOR, 1.03 per year; P = .024) were all significantly associated with poor adherence to lenalidomide.

The mean medication possession ratio among study patients was 89.5%. Overall, 38% of patients in the study had poor adherence to lenalidomide, while just 7% of patients in the study had a medication possession ratio of 100%, indicating “perfect adherence.”

There was a trend toward inferior overall survival among patients with poor adherence to lenalidomide, but it was not statistically significant (hazard ratio 1.10, 95% confidence interval, 0.88-1.38).

“Our study emphasizes the need for both better clinical monitoring of adherence and for future prospective studies in accurately understanding the rates and predictors of adherence while simultaneously developing strategies for improving adherence for patients that are at high risk of nonadherence,” the researchers wrote.

The National Institutes of Health funded the study. No conflicts of interest were reported.

SOURCE: Mian H et al. Clin Lymphoma Myeloma Leuk. 2019 Oct 9. doi: 10.1016/j.clml.2019.09.618.