Mantle Cell Lymphoma

At least four new trials in mantle cell lymphoma (MCL) are preparing to launch, according to records posted on Clinicaltrials.gov.

The range of new studies are occurring around the world and examine the association of lenalidomide with tumor flare reaction, maintenance ixazomib for newly diagnosed patients, the addition of bortezomib to ibrutinib in ibrutinib-released patients, and acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in untreated patients.

Acalabrutinib With Alternating Cycles of Bendamustine/Rituximab and Cytarabine/Rituximab for Untreated Mantle Cell Lymphoma (NCT03623373) is slated to start on Oct. 31, 2018, and be completed in 2025.

The trial, which is not yet recruiting, is estimated to enroll 15 participants. The phase 1 study will be aimed at evaluating the efficacy and safety of acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in MCL patients who are treatment naive. The primary outcome measure is stem cell mobilization success rate in patients treated with this regimen. The phase 1 study is preparation for a larger cooperative group trial that aims to achieve a standard induction regimen for MCL in transplant-eligible patients.

The study is sponsored by Washington University, St. Louis, in collaboration with Acerta Pharma.

Ibrutinib-relapsed MCL

Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma (NCT03617484) is scheduled to start in September 2018 and be completed in 2021. It is estimated to enroll 35 patients but is not yet recruiting.

The phase 2, open-label study is aimed at evaluating the efficacy of the ibrutinib/bortezomib in MCL patients who relapsed on ibrutinib alone. The primary outcome is the overall response rate at 6 months based on the Lugano criteria.

The trial is sponsored by the University of Michigan, Ann Arbor.

Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma (NCT03616782) launched in August 2018 and is expected to be completed in 2022.

The phase 2 trial is expected to enroll 98 patients but has not started recruitment yet. In the open-label, multicenter study, newly diagnosed MCL patients will receive induction chemotherapy and those who achieve at least a partial response will be eligible to move on to the experimental phase – maintenance ixazomib. At least 8 weeks after completing induction, patients can receive ixazomib orally on days 1, 8, and 15 for 4 weeks. Treatment repeats every 4 weeks for up to 2 years unless the disease progresses or there is unacceptable toxicity. The primary outcome measure is 2-year progression-free survival.

The trial is sponsored by Ho Sup Lee, MD, of Kosin University Gospel Hospital in Busan, South Korea, in collaboration with Takeda.

PASS MCL-005

The Noninterventional Study in Patients With Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL) to Investigate the Association of Lenalidomide With Tumor Flare Reaction and High Tumor Burden, called PASS MCL-005 (NCT03647124) is slated to start at the end of September 2018 and wrap up in 2026.

The retrospective cohort study will rely on data collection from Nordic registries and national health databases. The researchers will analyze records from sites where lenalidomide treatment for relapsed/refractory MCL is reimbursed. The estimated enrollment is 560 participants.

The primary goal is to quantify and characterize the event of tumor flare reaction by tumor burden in relapsed/refractory MCL patients who were treated with lenalidomide in a real-world setting.

The European-based study is sponsored by Celgene.

mschneider@mdedge.com

At least four new trials in mantle cell lymphoma (MCL) are preparing to launch, according to records posted on Clinicaltrials.gov.

The range of new studies are occurring around the world and examine the association of lenalidomide with tumor flare reaction, maintenance ixazomib for newly diagnosed patients, the addition of bortezomib to ibrutinib in ibrutinib-released patients, and acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in untreated patients.

Acalabrutinib With Alternating Cycles of Bendamustine/Rituximab and Cytarabine/Rituximab for Untreated Mantle Cell Lymphoma (NCT03623373) is slated to start on Oct. 31, 2018, and be completed in 2025.

The trial, which is not yet recruiting, is estimated to enroll 15 participants. The phase 1 study will be aimed at evaluating the efficacy and safety of acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in MCL patients who are treatment naive. The primary outcome measure is stem cell mobilization success rate in patients treated with this regimen. The phase 1 study is preparation for a larger cooperative group trial that aims to achieve a standard induction regimen for MCL in transplant-eligible patients.

The study is sponsored by Washington University, St. Louis, in collaboration with Acerta Pharma.

Ibrutinib-relapsed MCL

Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma (NCT03617484) is scheduled to start in September 2018 and be completed in 2021. It is estimated to enroll 35 patients but is not yet recruiting.

The phase 2, open-label study is aimed at evaluating the efficacy of the ibrutinib/bortezomib in MCL patients who relapsed on ibrutinib alone. The primary outcome is the overall response rate at 6 months based on the Lugano criteria.

The trial is sponsored by the University of Michigan, Ann Arbor.

Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma (NCT03616782) launched in August 2018 and is expected to be completed in 2022.

The phase 2 trial is expected to enroll 98 patients but has not started recruitment yet. In the open-label, multicenter study, newly diagnosed MCL patients will receive induction chemotherapy and those who achieve at least a partial response will be eligible to move on to the experimental phase – maintenance ixazomib. At least 8 weeks after completing induction, patients can receive ixazomib orally on days 1, 8, and 15 for 4 weeks. Treatment repeats every 4 weeks for up to 2 years unless the disease progresses or there is unacceptable toxicity. The primary outcome measure is 2-year progression-free survival.

The trial is sponsored by Ho Sup Lee, MD, of Kosin University Gospel Hospital in Busan, South Korea, in collaboration with Takeda.

PASS MCL-005

The Noninterventional Study in Patients With Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL) to Investigate the Association of Lenalidomide With Tumor Flare Reaction and High Tumor Burden, called PASS MCL-005 (NCT03647124) is slated to start at the end of September 2018 and wrap up in 2026.

The retrospective cohort study will rely on data collection from Nordic registries and national health databases. The researchers will analyze records from sites where lenalidomide treatment for relapsed/refractory MCL is reimbursed. The estimated enrollment is 560 participants.

The primary goal is to quantify and characterize the event of tumor flare reaction by tumor burden in relapsed/refractory MCL patients who were treated with lenalidomide in a real-world setting.

The European-based study is sponsored by Celgene.

mschneider@mdedge.com

At least four new trials in mantle cell lymphoma (MCL) are preparing to launch, according to records posted on Clinicaltrials.gov.

The range of new studies are occurring around the world and examine the association of lenalidomide with tumor flare reaction, maintenance ixazomib for newly diagnosed patients, the addition of bortezomib to ibrutinib in ibrutinib-released patients, and acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in untreated patients.

Acalabrutinib With Alternating Cycles of Bendamustine/Rituximab and Cytarabine/Rituximab for Untreated Mantle Cell Lymphoma (NCT03623373) is slated to start on Oct. 31, 2018, and be completed in 2025.

The trial, which is not yet recruiting, is estimated to enroll 15 participants. The phase 1 study will be aimed at evaluating the efficacy and safety of acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in MCL patients who are treatment naive. The primary outcome measure is stem cell mobilization success rate in patients treated with this regimen. The phase 1 study is preparation for a larger cooperative group trial that aims to achieve a standard induction regimen for MCL in transplant-eligible patients.

The study is sponsored by Washington University, St. Louis, in collaboration with Acerta Pharma.

Ibrutinib-relapsed MCL

Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma (NCT03617484) is scheduled to start in September 2018 and be completed in 2021. It is estimated to enroll 35 patients but is not yet recruiting.

The phase 2, open-label study is aimed at evaluating the efficacy of the ibrutinib/bortezomib in MCL patients who relapsed on ibrutinib alone. The primary outcome is the overall response rate at 6 months based on the Lugano criteria.

The trial is sponsored by the University of Michigan, Ann Arbor.

Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma (NCT03616782) launched in August 2018 and is expected to be completed in 2022.

The phase 2 trial is expected to enroll 98 patients but has not started recruitment yet. In the open-label, multicenter study, newly diagnosed MCL patients will receive induction chemotherapy and those who achieve at least a partial response will be eligible to move on to the experimental phase – maintenance ixazomib. At least 8 weeks after completing induction, patients can receive ixazomib orally on days 1, 8, and 15 for 4 weeks. Treatment repeats every 4 weeks for up to 2 years unless the disease progresses or there is unacceptable toxicity. The primary outcome measure is 2-year progression-free survival.

The trial is sponsored by Ho Sup Lee, MD, of Kosin University Gospel Hospital in Busan, South Korea, in collaboration with Takeda.

PASS MCL-005

The Noninterventional Study in Patients With Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL) to Investigate the Association of Lenalidomide With Tumor Flare Reaction and High Tumor Burden, called PASS MCL-005 (NCT03647124) is slated to start at the end of September 2018 and wrap up in 2026.

The retrospective cohort study will rely on data collection from Nordic registries and national health databases. The researchers will analyze records from sites where lenalidomide treatment for relapsed/refractory MCL is reimbursed. The estimated enrollment is 560 participants.

The primary goal is to quantify and characterize the event of tumor flare reaction by tumor burden in relapsed/refractory MCL patients who were treated with lenalidomide in a real-world setting.

The European-based study is sponsored by Celgene.

mschneider@mdedge.com

An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.

Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.

However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.

Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.

SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.

Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.

The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.

Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.

The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.

Other common AEs were nausea and fatigue.

The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.

The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.

The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.

SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.

An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.

Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.

However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.

Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.

SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.

Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.

The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.

Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.

The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.

Other common AEs were nausea and fatigue.

The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.

The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.

The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.

SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.

An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.

Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.

However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.

Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.

SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.

Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.

The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.

Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.

The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.

Other common AEs were nausea and fatigue.

The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.

The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.

The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.

SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.

The China Drug Administration is reviewing the Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib for the treatment of relapsed/refractory mantle cell lymphoma (MCL).

The U.S. Food and Drug Administration recently granted the drug fast track designation for the treatment of patients with Waldenström’s macroglobulinemia.

The application in China is supported by results from a phase 2, single-arm trial of 86 patients with relapsed/refractory MCL who received 160 mg zanubrutinib orally twice daily. The overall response rate was 84%, which included 59% of patients with a complete response. At 8.3 months of follow-up, the median duration of response had not been reached, according to the drug’s sponsor BeiGene.

Zanubrutinib is being studied in several ongoing trials, including for the treatment of untreated chronic lymphocytic leukemia (CLL), for relapsed/refractory follicular lymphoma in combination with obinutuzumab, and comparing it to ibrutinib in Waldenström’s macroglobulinemia and CLL/small lymphocytic lymphoma.

mschneider@mdedge.com

The China Drug Administration is reviewing the Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib for the treatment of relapsed/refractory mantle cell lymphoma (MCL).

The U.S. Food and Drug Administration recently granted the drug fast track designation for the treatment of patients with Waldenström’s macroglobulinemia.

The application in China is supported by results from a phase 2, single-arm trial of 86 patients with relapsed/refractory MCL who received 160 mg zanubrutinib orally twice daily. The overall response rate was 84%, which included 59% of patients with a complete response. At 8.3 months of follow-up, the median duration of response had not been reached, according to the drug’s sponsor BeiGene.

Zanubrutinib is being studied in several ongoing trials, including for the treatment of untreated chronic lymphocytic leukemia (CLL), for relapsed/refractory follicular lymphoma in combination with obinutuzumab, and comparing it to ibrutinib in Waldenström’s macroglobulinemia and CLL/small lymphocytic lymphoma.

mschneider@mdedge.com

The China Drug Administration is reviewing the Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib for the treatment of relapsed/refractory mantle cell lymphoma (MCL).

The U.S. Food and Drug Administration recently granted the drug fast track designation for the treatment of patients with Waldenström’s macroglobulinemia.

The application in China is supported by results from a phase 2, single-arm trial of 86 patients with relapsed/refractory MCL who received 160 mg zanubrutinib orally twice daily. The overall response rate was 84%, which included 59% of patients with a complete response. At 8.3 months of follow-up, the median duration of response had not been reached, according to the drug’s sponsor BeiGene.

Zanubrutinib is being studied in several ongoing trials, including for the treatment of untreated chronic lymphocytic leukemia (CLL), for relapsed/refractory follicular lymphoma in combination with obinutuzumab, and comparing it to ibrutinib in Waldenström’s macroglobulinemia and CLL/small lymphocytic lymphoma.

mschneider@mdedge.com

Patients with mantle cell lymphoma (MCL) have better outcomes if they receive rituximab (Rituxan) maintenance therapy after induction therapy, albeit with the trade-off of higher risk of neutropenia, according to results of a meta-analysis reported in HemaSphere.

Investigators led by Liat Vidal, MD, of Tel-Aviv University, analyzed data from six randomized controlled trials of maintenance therapy including 858 patients with MCL who had a complete or partial response to induction therapy. The maintenance therapy was rituximab in five trials and bortezomib (Velcade) in one trial. The median duration of follow-up was 26-59 months across trials.

Main results showed that, compared with patients who were simply observed or given maintenance interferon-alfa, those given maintenance rituximab had a significantly reduced risk of progression or death (pooled hazard ratio, 0.58; 95% confidence interval, 0.45-0.73) and a nonsignificantly reduced risk of death (pHR, 0.79; 95% CI, 0.58-1.06).

Rituximab maintenance therapy was associated with a doubling of the risk of grade 3 or 4 neutropenia (risk ratio, 2.02; 95% CI, 1.50-2.73). However, there was no significant difference between groups with respect to risks of infection, or grade 3 or 4 anemia or thrombocythemia.

None of the included trials reported on quality of life outcomes.

The lone trial of bortezomib maintenance did not find any significant event-free survival or overall survival benefit.

“Based on our results, rituximab maintenance is recommended after immunochemotherapy with R-CHOP or cytarabine-containing induction in the front-line setting for transplant-eligible and -ineligible patients, and after R-CHOP in the relapse setting. It is unclear if maintenance is of benefit after different induction chemotherapy such as bendamustine or fludarabine,” Dr. Vidal and coauthors conclude. “By contrast, current data does not support improved outcomes with bortezomib maintenance for MCL patients.”

Dr. Vidal disclosed that she is an employee of Syneos Health. The study received no funding.

SOURCE: Vidal L et al. HemaSphere. 2018 Aug;2(4):e136.

Patients with mantle cell lymphoma (MCL) have better outcomes if they receive rituximab (Rituxan) maintenance therapy after induction therapy, albeit with the trade-off of higher risk of neutropenia, according to results of a meta-analysis reported in HemaSphere.

Investigators led by Liat Vidal, MD, of Tel-Aviv University, analyzed data from six randomized controlled trials of maintenance therapy including 858 patients with MCL who had a complete or partial response to induction therapy. The maintenance therapy was rituximab in five trials and bortezomib (Velcade) in one trial. The median duration of follow-up was 26-59 months across trials.

Main results showed that, compared with patients who were simply observed or given maintenance interferon-alfa, those given maintenance rituximab had a significantly reduced risk of progression or death (pooled hazard ratio, 0.58; 95% confidence interval, 0.45-0.73) and a nonsignificantly reduced risk of death (pHR, 0.79; 95% CI, 0.58-1.06).

Rituximab maintenance therapy was associated with a doubling of the risk of grade 3 or 4 neutropenia (risk ratio, 2.02; 95% CI, 1.50-2.73). However, there was no significant difference between groups with respect to risks of infection, or grade 3 or 4 anemia or thrombocythemia.

None of the included trials reported on quality of life outcomes.

The lone trial of bortezomib maintenance did not find any significant event-free survival or overall survival benefit.

“Based on our results, rituximab maintenance is recommended after immunochemotherapy with R-CHOP or cytarabine-containing induction in the front-line setting for transplant-eligible and -ineligible patients, and after R-CHOP in the relapse setting. It is unclear if maintenance is of benefit after different induction chemotherapy such as bendamustine or fludarabine,” Dr. Vidal and coauthors conclude. “By contrast, current data does not support improved outcomes with bortezomib maintenance for MCL patients.”

Dr. Vidal disclosed that she is an employee of Syneos Health. The study received no funding.

SOURCE: Vidal L et al. HemaSphere. 2018 Aug;2(4):e136.

Patients with mantle cell lymphoma (MCL) have better outcomes if they receive rituximab (Rituxan) maintenance therapy after induction therapy, albeit with the trade-off of higher risk of neutropenia, according to results of a meta-analysis reported in HemaSphere.

Investigators led by Liat Vidal, MD, of Tel-Aviv University, analyzed data from six randomized controlled trials of maintenance therapy including 858 patients with MCL who had a complete or partial response to induction therapy. The maintenance therapy was rituximab in five trials and bortezomib (Velcade) in one trial. The median duration of follow-up was 26-59 months across trials.

Main results showed that, compared with patients who were simply observed or given maintenance interferon-alfa, those given maintenance rituximab had a significantly reduced risk of progression or death (pooled hazard ratio, 0.58; 95% confidence interval, 0.45-0.73) and a nonsignificantly reduced risk of death (pHR, 0.79; 95% CI, 0.58-1.06).

Rituximab maintenance therapy was associated with a doubling of the risk of grade 3 or 4 neutropenia (risk ratio, 2.02; 95% CI, 1.50-2.73). However, there was no significant difference between groups with respect to risks of infection, or grade 3 or 4 anemia or thrombocythemia.

None of the included trials reported on quality of life outcomes.

The lone trial of bortezomib maintenance did not find any significant event-free survival or overall survival benefit.

“Based on our results, rituximab maintenance is recommended after immunochemotherapy with R-CHOP or cytarabine-containing induction in the front-line setting for transplant-eligible and -ineligible patients, and after R-CHOP in the relapse setting. It is unclear if maintenance is of benefit after different induction chemotherapy such as bendamustine or fludarabine,” Dr. Vidal and coauthors conclude. “By contrast, current data does not support improved outcomes with bortezomib maintenance for MCL patients.”

Dr. Vidal disclosed that she is an employee of Syneos Health. The study received no funding.

SOURCE: Vidal L et al. HemaSphere. 2018 Aug;2(4):e136.

Bone marrow involvement in mantle cell lymphoma could be assessed using just ¹⁸fluorodeoxyglucose (FDG)–PET/CT, according to findings from a small, retrospective study published in Clinical Lymphoma, Myeloma & Leukemia.

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Rustain Morgan, MD, of the University of Colorado, Aurora, and his colleagues found that, at a certain threshold of bone marrow voxels in standard uptake value (SUV), there was 100% sensitivity and 80% specificity in determining bone marrow involvement in mantle cell lymphoma (MCL).

Currently, National Comprehensive Cancer Network guidelines call for bone marrow biopsy and whole body FDG PET/CT scan to complete an initial diagnosis of MCL.

“One of the most important factors for correct staging is the identification of bone marrow involvement, occurring in approximately 55% of patients with MCL, which classifies patients as advanced stage. However, accurate analysis of bone marrow involvement can be challenging due to sampling error,” the researchers wrote. “While bone marrow biopsy remains the gold standard, it is not a perfect standard given unilateral variability.”

In previous studies, FDG PET/CT was not considered sensitive enough to detect gastrointestinal or bone marrow involvement. However, these earlier studies used SUV maximum or mean or a visual assessment of the bone marrow activity, compared with hepatic uptake. To address this issue, the researchers developed a new method of examining SUV distribution throughout the pelvic bones by analyzing thousands of bone marrow voxels within the bilateral iliacs.

During the developmental phase, an institutional dataset of 11 patients with MCL was used to define the voxel-based analysis. These patients had undergone both unilateral iliac bone marrow biopsy and FDG PET/CT at the initial diagnosis. Then, FDG PET/CT scans from another 12 patients with MCL from a different institution were used to validate the developmental phase findings. Finally, a control group of 5 people with no known malignancy were referred for FDG PET/CT pulmonary nodule evaluation.

“The hypothesis of the study was that, if the bone marrow was involved by lymphoma, then there would be a small increase in the SUV of each voxel, reflecting involvement by the lymphoma. In order to capture such changes, we analyzed the percent of total voxels in SUV ranging from 0.75 to 1.20, in increments of 0.05, as this is where the greatest divergence was visually identified,” the researchers wrote. “The goal was to identify if a percentage of voxels at a set SUV could detect lymphomatous involvement.”

The researchers identified 10 candidate thresholds in the developmental phase; 4 of these performed better than the others in the validation phase. Using those thresholds, 10 of the 12 patients in the validation cohort could be correctly staged using FDG PET/CT.

Further analysis identified a single threshold that performed best: If greater than 38% of the voxels (averaging 1,734 voxels) demonstrated an SUV of less than 0.95, the sensitivity was 100% and the specificity was 80%.

The researchers acknowledged that the findings are limited because of the study’s small sample size and said the results should be validated in a larger trial.

There was no external funding for the study and the researchers reported having no financial disclosures.

mschneider@mdedge.com

SOURCE: Morgan R et al. Clin Lymphoma Myeloma Leuk. 2018 Jul 4. doi: 10.1016/j.clml.2018.06.024.

Bone marrow involvement in mantle cell lymphoma could be assessed using just ¹⁸fluorodeoxyglucose (FDG)–PET/CT, according to findings from a small, retrospective study published in Clinical Lymphoma, Myeloma & Leukemia.

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Rustain Morgan, MD, of the University of Colorado, Aurora, and his colleagues found that, at a certain threshold of bone marrow voxels in standard uptake value (SUV), there was 100% sensitivity and 80% specificity in determining bone marrow involvement in mantle cell lymphoma (MCL).

Currently, National Comprehensive Cancer Network guidelines call for bone marrow biopsy and whole body FDG PET/CT scan to complete an initial diagnosis of MCL.

“One of the most important factors for correct staging is the identification of bone marrow involvement, occurring in approximately 55% of patients with MCL, which classifies patients as advanced stage. However, accurate analysis of bone marrow involvement can be challenging due to sampling error,” the researchers wrote. “While bone marrow biopsy remains the gold standard, it is not a perfect standard given unilateral variability.”

In previous studies, FDG PET/CT was not considered sensitive enough to detect gastrointestinal or bone marrow involvement. However, these earlier studies used SUV maximum or mean or a visual assessment of the bone marrow activity, compared with hepatic uptake. To address this issue, the researchers developed a new method of examining SUV distribution throughout the pelvic bones by analyzing thousands of bone marrow voxels within the bilateral iliacs.

During the developmental phase, an institutional dataset of 11 patients with MCL was used to define the voxel-based analysis. These patients had undergone both unilateral iliac bone marrow biopsy and FDG PET/CT at the initial diagnosis. Then, FDG PET/CT scans from another 12 patients with MCL from a different institution were used to validate the developmental phase findings. Finally, a control group of 5 people with no known malignancy were referred for FDG PET/CT pulmonary nodule evaluation.

“The hypothesis of the study was that, if the bone marrow was involved by lymphoma, then there would be a small increase in the SUV of each voxel, reflecting involvement by the lymphoma. In order to capture such changes, we analyzed the percent of total voxels in SUV ranging from 0.75 to 1.20, in increments of 0.05, as this is where the greatest divergence was visually identified,” the researchers wrote. “The goal was to identify if a percentage of voxels at a set SUV could detect lymphomatous involvement.”

The researchers identified 10 candidate thresholds in the developmental phase; 4 of these performed better than the others in the validation phase. Using those thresholds, 10 of the 12 patients in the validation cohort could be correctly staged using FDG PET/CT.

Further analysis identified a single threshold that performed best: If greater than 38% of the voxels (averaging 1,734 voxels) demonstrated an SUV of less than 0.95, the sensitivity was 100% and the specificity was 80%.

The researchers acknowledged that the findings are limited because of the study’s small sample size and said the results should be validated in a larger trial.

There was no external funding for the study and the researchers reported having no financial disclosures.

mschneider@mdedge.com

SOURCE: Morgan R et al. Clin Lymphoma Myeloma Leuk. 2018 Jul 4. doi: 10.1016/j.clml.2018.06.024.

Bone marrow involvement in mantle cell lymphoma could be assessed using just ¹⁸fluorodeoxyglucose (FDG)–PET/CT, according to findings from a small, retrospective study published in Clinical Lymphoma, Myeloma & Leukemia.

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Rustain Morgan, MD, of the University of Colorado, Aurora, and his colleagues found that, at a certain threshold of bone marrow voxels in standard uptake value (SUV), there was 100% sensitivity and 80% specificity in determining bone marrow involvement in mantle cell lymphoma (MCL).

Currently, National Comprehensive Cancer Network guidelines call for bone marrow biopsy and whole body FDG PET/CT scan to complete an initial diagnosis of MCL.

“One of the most important factors for correct staging is the identification of bone marrow involvement, occurring in approximately 55% of patients with MCL, which classifies patients as advanced stage. However, accurate analysis of bone marrow involvement can be challenging due to sampling error,” the researchers wrote. “While bone marrow biopsy remains the gold standard, it is not a perfect standard given unilateral variability.”

In previous studies, FDG PET/CT was not considered sensitive enough to detect gastrointestinal or bone marrow involvement. However, these earlier studies used SUV maximum or mean or a visual assessment of the bone marrow activity, compared with hepatic uptake. To address this issue, the researchers developed a new method of examining SUV distribution throughout the pelvic bones by analyzing thousands of bone marrow voxels within the bilateral iliacs.

During the developmental phase, an institutional dataset of 11 patients with MCL was used to define the voxel-based analysis. These patients had undergone both unilateral iliac bone marrow biopsy and FDG PET/CT at the initial diagnosis. Then, FDG PET/CT scans from another 12 patients with MCL from a different institution were used to validate the developmental phase findings. Finally, a control group of 5 people with no known malignancy were referred for FDG PET/CT pulmonary nodule evaluation.

“The hypothesis of the study was that, if the bone marrow was involved by lymphoma, then there would be a small increase in the SUV of each voxel, reflecting involvement by the lymphoma. In order to capture such changes, we analyzed the percent of total voxels in SUV ranging from 0.75 to 1.20, in increments of 0.05, as this is where the greatest divergence was visually identified,” the researchers wrote. “The goal was to identify if a percentage of voxels at a set SUV could detect lymphomatous involvement.”

The researchers identified 10 candidate thresholds in the developmental phase; 4 of these performed better than the others in the validation phase. Using those thresholds, 10 of the 12 patients in the validation cohort could be correctly staged using FDG PET/CT.

Further analysis identified a single threshold that performed best: If greater than 38% of the voxels (averaging 1,734 voxels) demonstrated an SUV of less than 0.95, the sensitivity was 100% and the specificity was 80%.

The researchers acknowledged that the findings are limited because of the study’s small sample size and said the results should be validated in a larger trial.

There was no external funding for the study and the researchers reported having no financial disclosures.

mschneider@mdedge.com

SOURCE: Morgan R et al. Clin Lymphoma Myeloma Leuk. 2018 Jul 4. doi: 10.1016/j.clml.2018.06.024.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Rituximab should be included in first-line chemotherapy when treating mantle cell lymphoma, according to a new management guideline from the British Society for Haematology.

The best outcome data is for the R-CHOP regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by maintenance treatment with rituximab, wrote Pamela McKay, MD, of Beatson West of Scotland Cancer Centre in Glasgow, and her colleagues. The report was published in the British Journal of Haematology. But the combination of rituximab and bendamustine is also effective and a more favorable safety profile, according to the guideline. Single agent rituximab is not recommended.

At relapse, the guideline calls on physicians to take an individualized approach based on age, comorbidities, performance status, and response to prior therapy. Some options to consider include ibrutinib as a single agent or rituximab plus chemotherapy. The authors cautioned that there is little evidence to support maintenance rituximab after relapse treatment.

The guideline also explores the role of autologous stem cell transplantation (ASCT) and allogeneic SCT (alloSCT). The authors recommend that ASCT be considered as consolidation of first-line therapy for patients who are fit for intensive therapy. AlloSCT is a viable option in second remission among fit patients who have an appropriate donor and it may also be effective as a rescue therapy for patients who relapse after ASCT. But alloSCT is appropriate only as a first-line therapy for high-risk patients and is best used as part of a clinical trial, according to the recommendations.

The British Society of Haematology previously issued guidance on mantle cell lymphoma in 2012, but the updated document includes new drug therapeutic options and transplant data. The guideline includes a therapeutic algorithm to assist physicians in choosing first-line therapy, options after first relapse, and management in the case of higher relapse.

The guideline authors reported having no conflicts of interest.

mschneider@mdedge.com

SOURCE: McKay P et al. Br J Haematol. 2018 Jul;182(1):46-62.

Rituximab should be included in first-line chemotherapy when treating mantle cell lymphoma, according to a new management guideline from the British Society for Haematology.

The best outcome data is for the R-CHOP regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by maintenance treatment with rituximab, wrote Pamela McKay, MD, of Beatson West of Scotland Cancer Centre in Glasgow, and her colleagues. The report was published in the British Journal of Haematology. But the combination of rituximab and bendamustine is also effective and a more favorable safety profile, according to the guideline. Single agent rituximab is not recommended.

At relapse, the guideline calls on physicians to take an individualized approach based on age, comorbidities, performance status, and response to prior therapy. Some options to consider include ibrutinib as a single agent or rituximab plus chemotherapy. The authors cautioned that there is little evidence to support maintenance rituximab after relapse treatment.

The guideline also explores the role of autologous stem cell transplantation (ASCT) and allogeneic SCT (alloSCT). The authors recommend that ASCT be considered as consolidation of first-line therapy for patients who are fit for intensive therapy. AlloSCT is a viable option in second remission among fit patients who have an appropriate donor and it may also be effective as a rescue therapy for patients who relapse after ASCT. But alloSCT is appropriate only as a first-line therapy for high-risk patients and is best used as part of a clinical trial, according to the recommendations.

The British Society of Haematology previously issued guidance on mantle cell lymphoma in 2012, but the updated document includes new drug therapeutic options and transplant data. The guideline includes a therapeutic algorithm to assist physicians in choosing first-line therapy, options after first relapse, and management in the case of higher relapse.

The guideline authors reported having no conflicts of interest.

mschneider@mdedge.com

SOURCE: McKay P et al. Br J Haematol. 2018 Jul;182(1):46-62.

Rituximab should be included in first-line chemotherapy when treating mantle cell lymphoma, according to a new management guideline from the British Society for Haematology.

The best outcome data is for the R-CHOP regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by maintenance treatment with rituximab, wrote Pamela McKay, MD, of Beatson West of Scotland Cancer Centre in Glasgow, and her colleagues. The report was published in the British Journal of Haematology. But the combination of rituximab and bendamustine is also effective and a more favorable safety profile, according to the guideline. Single agent rituximab is not recommended.

At relapse, the guideline calls on physicians to take an individualized approach based on age, comorbidities, performance status, and response to prior therapy. Some options to consider include ibrutinib as a single agent or rituximab plus chemotherapy. The authors cautioned that there is little evidence to support maintenance rituximab after relapse treatment.

The guideline also explores the role of autologous stem cell transplantation (ASCT) and allogeneic SCT (alloSCT). The authors recommend that ASCT be considered as consolidation of first-line therapy for patients who are fit for intensive therapy. AlloSCT is a viable option in second remission among fit patients who have an appropriate donor and it may also be effective as a rescue therapy for patients who relapse after ASCT. But alloSCT is appropriate only as a first-line therapy for high-risk patients and is best used as part of a clinical trial, according to the recommendations.

The British Society of Haematology previously issued guidance on mantle cell lymphoma in 2012, but the updated document includes new drug therapeutic options and transplant data. The guideline includes a therapeutic algorithm to assist physicians in choosing first-line therapy, options after first relapse, and management in the case of higher relapse.

The guideline authors reported having no conflicts of interest.

mschneider@mdedge.com

SOURCE: McKay P et al. Br J Haematol. 2018 Jul;182(1):46-62.

Combining bortezomib with vorinostat produced a modest overall response in mantle cell lymphoma (MCL) patients, but was less impressive among patients with diffuse large B-cell lymphoma (DLBCL).

Victor Yazbeck, MD, of the Massey Cancer Center at Virginia Commonwealth University in Richmond, and his colleagues reported the findings from the multicenter, nonrandomized, phase 2 trial with 65 treated patients. The trial included three cohorts: 22 patients with MCL and no prior treatment with bortezomib; 4 patients with MCL and prior treatment with bortezomib; and 39 patients with relapsed or refractory DLBCL and no prior bortezomib.

The best results were seen among MCL patients with no prior bortezomib treatment, with an overall response rate of 31.8% and a median progression-free survival (PFS) of 7.6 months. Responses were limited among the DLBCL cohort, which had an overall response rate of 7.7% and a median PFS of just 1.8 months. Among MCL patients who had received prior bortezomib treatment, there were no responses.

From a safety perspective, the combination treatment was well tolerated. The most common grade 3 and 4 hematologic toxicities were thrombocytopenia, lymphopenia, and neutropenia. There was one death among the DLBCL patients and it was unclear if it was related to treatment or progression of disease.

“Patients with MCL had a higher [overall response rate] compared to those with DLBCL, most likely due to the single-agent activity of bortezomib in MCL,” the researchers wrote. “Overall, the synergism previously demonstrated in preclinical models could not be confirmed.”

The study was supported by the Southeast Phase 2 Consortium and by a grant from the National Cancer Institute. Dr. Yazbeck reported having no financial disclosures. One of his coauthors is an employee of Amgen and owns Amgen stock. Another coauthor receives research support from Takeda, Celgene, Karyopharm Therapeutics, Bristol-Myers Squibb, Merck, and Signal Genetics.

mschneider@mdedge.com

SOURCE: Yazbeck V et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 6. doi: 10.1016/j.clml.2018.05.023.

Combining bortezomib with vorinostat produced a modest overall response in mantle cell lymphoma (MCL) patients, but was less impressive among patients with diffuse large B-cell lymphoma (DLBCL).

Victor Yazbeck, MD, of the Massey Cancer Center at Virginia Commonwealth University in Richmond, and his colleagues reported the findings from the multicenter, nonrandomized, phase 2 trial with 65 treated patients. The trial included three cohorts: 22 patients with MCL and no prior treatment with bortezomib; 4 patients with MCL and prior treatment with bortezomib; and 39 patients with relapsed or refractory DLBCL and no prior bortezomib.

The best results were seen among MCL patients with no prior bortezomib treatment, with an overall response rate of 31.8% and a median progression-free survival (PFS) of 7.6 months. Responses were limited among the DLBCL cohort, which had an overall response rate of 7.7% and a median PFS of just 1.8 months. Among MCL patients who had received prior bortezomib treatment, there were no responses.

From a safety perspective, the combination treatment was well tolerated. The most common grade 3 and 4 hematologic toxicities were thrombocytopenia, lymphopenia, and neutropenia. There was one death among the DLBCL patients and it was unclear if it was related to treatment or progression of disease.

“Patients with MCL had a higher [overall response rate] compared to those with DLBCL, most likely due to the single-agent activity of bortezomib in MCL,” the researchers wrote. “Overall, the synergism previously demonstrated in preclinical models could not be confirmed.”

The study was supported by the Southeast Phase 2 Consortium and by a grant from the National Cancer Institute. Dr. Yazbeck reported having no financial disclosures. One of his coauthors is an employee of Amgen and owns Amgen stock. Another coauthor receives research support from Takeda, Celgene, Karyopharm Therapeutics, Bristol-Myers Squibb, Merck, and Signal Genetics.

mschneider@mdedge.com

SOURCE: Yazbeck V et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 6. doi: 10.1016/j.clml.2018.05.023.

Combining bortezomib with vorinostat produced a modest overall response in mantle cell lymphoma (MCL) patients, but was less impressive among patients with diffuse large B-cell lymphoma (DLBCL).

Victor Yazbeck, MD, of the Massey Cancer Center at Virginia Commonwealth University in Richmond, and his colleagues reported the findings from the multicenter, nonrandomized, phase 2 trial with 65 treated patients. The trial included three cohorts: 22 patients with MCL and no prior treatment with bortezomib; 4 patients with MCL and prior treatment with bortezomib; and 39 patients with relapsed or refractory DLBCL and no prior bortezomib.

The best results were seen among MCL patients with no prior bortezomib treatment, with an overall response rate of 31.8% and a median progression-free survival (PFS) of 7.6 months. Responses were limited among the DLBCL cohort, which had an overall response rate of 7.7% and a median PFS of just 1.8 months. Among MCL patients who had received prior bortezomib treatment, there were no responses.

From a safety perspective, the combination treatment was well tolerated. The most common grade 3 and 4 hematologic toxicities were thrombocytopenia, lymphopenia, and neutropenia. There was one death among the DLBCL patients and it was unclear if it was related to treatment or progression of disease.

“Patients with MCL had a higher [overall response rate] compared to those with DLBCL, most likely due to the single-agent activity of bortezomib in MCL,” the researchers wrote. “Overall, the synergism previously demonstrated in preclinical models could not be confirmed.”

The study was supported by the Southeast Phase 2 Consortium and by a grant from the National Cancer Institute. Dr. Yazbeck reported having no financial disclosures. One of his coauthors is an employee of Amgen and owns Amgen stock. Another coauthor receives research support from Takeda, Celgene, Karyopharm Therapeutics, Bristol-Myers Squibb, Merck, and Signal Genetics.

mschneider@mdedge.com

SOURCE: Yazbeck V et al. Clin Lymphoma Myeloma Leuk. 2018 Jun 6. doi: 10.1016/j.clml.2018.05.023.

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

mschneider@mdedge.com

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

mschneider@mdedge.com

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

mschneider@mdedge.com

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.