Mantle Cell Lymphoma

CHICAGO – The treatment options for patients with mantle cell lymphoma (MCL) vary based on age, but several prognostic factors can help guide treatment decision making in all patients, according to Kristie A. Blum, MD.

These include age, disease stage, disease sites, Mantle Cell Lymphoma International Prognostic Index (MIPI), biologic factors, and histology, Dr. Blum said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

Age

“I think the most important thing to recognize is there really isn’t any randomized transplant data for patients that are over 65. … There are very few transplant studies for patients [aged] 66-70,” said Dr. Blum, acting professor of hematology and medical oncology at Emory University in Atlanta.

The SWOG 0213 study did examine rituximab-hyperCVAD (R-HCVAD) in this age group, and showed that it has higher toxicity and lower efficacy in older versus younger patients, she said.

“Of course this is not typically a transplant approach, but an intensive-therapy approach,” she said, noting that progression-free and overall survival in patients aged 66-70 years were just 29% and 57%, respectively (Ann Oncol. 2013 Jun; 24[6]:1587-93).

Stage

Like age, disease stage in MCL patients has not been well studied, Dr. Blum said.

“Most of the randomized transplant studies have been conducted in patients stage II-IV, so we don’t have a lot of data about the early-stage patients,” she said, adding, however, that there are some retrospective data on radiation therapy for stage I-II MCL in older adults.

An International Lymphoma Radiation Oncology Group study of 179 patients, for example, showed that overall survival was “really the same whether they got chemo, chemo plus radiation, or radiation alone,” she said.

The 10-year freedom from progression was 46%, 43%, and 31%, respectively (P = .64).
 

Location

“What about where the disease presents? We’ve all heard about indolent mantle cell – so there’s this leukemic ‘non-nodal’ variant that’s been described,” she said, noting that this variant has a chronic lymphocytic leukemia–like presentation (no nodal disease, blood and marrow involvement, and splenic involvement). “And they tend to be SOX11-negative with mutated [immunoglobulin variable region heavy chain gene].”

Another variant involves primarily nodal disease that typically presents without elevated white blood cell count, with low Ki-67 (10% or lower), with SOX11 positivity, and without TP53 mutations.

“But I would caution you that this is really not very well defined; there’s no clear marker that predicts for indolent disease,” Dr. Blum said. “If you have one of these patients and you’re thinking about observing them, my experience has been that the most important thing to do is make sure you look at their [gastrointestinal] tract. I’ve had a lot of these patients progress with colon masses over time.”
 

MIPI

MIPI is basically a risk score calculated based on age, performance status, lactate dehydrogenase levels, and white cell count, she said.

MIPI less than 5.70 indicates low risk, MIPI of 5.70-6.2 is considered intermediate risk, and MIPI greater than 6.2 is considered high risk. High-risk patients who were transplanted in one study had a median overall survival of about 2.8 years and a median time to treatment failure of 1.4 years (J Clin Oncol. 2014 May 1;32[13]:1338-46). Even among patients under age 65 with high risk, the median time to treatment failure was 2 years, she said.

“So I do wonder, are we really helping these patients by transplanting them?” she added. “Similarly, the low-risk patients had a median time to treatment failure of 6 years; I wonder if they didn’t need a transplant.”

Biology

Ki-67 protein, a cellular marker for proliferation, is another important prognostic factor. A European Mantle Cell network study showed that median overall survival for patients with a Ki-67 proliferation index of less than 30% was not reached, and 5-year survival was 75%. At the same time, the median overall survival (OS) for those with Ki-67 proliferation index of 30% or greater was just 3.4 years, and 5-year OS was only 41% (J Clin Oncol. 2016 Apr 20;34[12]:1386-94).

The prognostic effect was independent of induction treatment, Dr. Blum said.

Combining MIPI and the Ki-67 index (MIPI-C) provides further value in defining a very high-risk group; those with both high MIPI and high Ki-67 had a median overall survival of only 1.5 years, and those with both, but who were under age 65, had median OS of only 1.7 years.
 

Histology

Patients with blastoid MCL variants were shown in that same study to have median OS of about 2.8 years, compared with 8 years in those with nonblastoid variants. The 5-year OS and progression-free survival (PFS) for blastoid variants were 35% and 29%, respectively, and for nonblastoid variants were 68% and 44%, respectively.

“But when you look at this with respect to the Ki-67 – so those patients that were called nonblastoid, that had a high Ki-67 index – their median overall survival is still lower at 5 years,” she said, noting that median OS was not reached in blastic variant (low-Ki-67) patients. “So it seems like the prognostic effect of cytology is largely explained by the Ki-67 index.”

In terms of karyotype, several studies have shown that complex karyotype is associated with poorer outcomes. One recent multicenter study of 274 patients showed that median OS in 53 patients with at least three cytogenetic abnormalities versus the remaining patients was 4.5 years vs. 11.6 years, and median PFS was 1.9 vs. 4.4 years (Cancer. 2018 Jun 1;124[11]:2306-15).

TP53 deletions (which affect about 20% of MCL patients) and mutations (which affect about 10%), are also useful prognostic factors, she said, noting that each is associated with inferior outcomes, and in one study patients with both appeared to have the worst outcomes (Blood. 2017;130:1903-10).

Another study showed that high TP53 staining (greater than 50% positive) is also associated with inferior outcomes, including reduced time to treatment failure and lower overall survival (Blood. 2018;131:417-20).

Finally, the most important factor is the patient’s wishes, Dr. Blum said, noting that she has “a lot of long discussions with these patients.”

“I consider all of these factors with each patient that I see with mantle cell,” she said.

Dr. Blum is a consultant for Acerta, AstraZeneca, and Molecular Templates and has received research funding from Acerta, AstraZeneca, Celgene, Cephalon, Immunomedics, Janssen, Merck, Millennium, Molecular Templates, Novartis, Pharmacyclics, and Seattle Genetics.

[email protected]

CHICAGO – The treatment options for patients with mantle cell lymphoma (MCL) vary based on age, but several prognostic factors can help guide treatment decision making in all patients, according to Kristie A. Blum, MD.

These include age, disease stage, disease sites, Mantle Cell Lymphoma International Prognostic Index (MIPI), biologic factors, and histology, Dr. Blum said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

Age

“I think the most important thing to recognize is there really isn’t any randomized transplant data for patients that are over 65. … There are very few transplant studies for patients [aged] 66-70,” said Dr. Blum, acting professor of hematology and medical oncology at Emory University in Atlanta.

The SWOG 0213 study did examine rituximab-hyperCVAD (R-HCVAD) in this age group, and showed that it has higher toxicity and lower efficacy in older versus younger patients, she said.

“Of course this is not typically a transplant approach, but an intensive-therapy approach,” she said, noting that progression-free and overall survival in patients aged 66-70 years were just 29% and 57%, respectively (Ann Oncol. 2013 Jun; 24[6]:1587-93).

Stage

Like age, disease stage in MCL patients has not been well studied, Dr. Blum said.

“Most of the randomized transplant studies have been conducted in patients stage II-IV, so we don’t have a lot of data about the early-stage patients,” she said, adding, however, that there are some retrospective data on radiation therapy for stage I-II MCL in older adults.

An International Lymphoma Radiation Oncology Group study of 179 patients, for example, showed that overall survival was “really the same whether they got chemo, chemo plus radiation, or radiation alone,” she said.

The 10-year freedom from progression was 46%, 43%, and 31%, respectively (P = .64).
 

Location

“What about where the disease presents? We’ve all heard about indolent mantle cell – so there’s this leukemic ‘non-nodal’ variant that’s been described,” she said, noting that this variant has a chronic lymphocytic leukemia–like presentation (no nodal disease, blood and marrow involvement, and splenic involvement). “And they tend to be SOX11-negative with mutated [immunoglobulin variable region heavy chain gene].”

Another variant involves primarily nodal disease that typically presents without elevated white blood cell count, with low Ki-67 (10% or lower), with SOX11 positivity, and without TP53 mutations.

“But I would caution you that this is really not very well defined; there’s no clear marker that predicts for indolent disease,” Dr. Blum said. “If you have one of these patients and you’re thinking about observing them, my experience has been that the most important thing to do is make sure you look at their [gastrointestinal] tract. I’ve had a lot of these patients progress with colon masses over time.”
 

MIPI

MIPI is basically a risk score calculated based on age, performance status, lactate dehydrogenase levels, and white cell count, she said.

MIPI less than 5.70 indicates low risk, MIPI of 5.70-6.2 is considered intermediate risk, and MIPI greater than 6.2 is considered high risk. High-risk patients who were transplanted in one study had a median overall survival of about 2.8 years and a median time to treatment failure of 1.4 years (J Clin Oncol. 2014 May 1;32[13]:1338-46). Even among patients under age 65 with high risk, the median time to treatment failure was 2 years, she said.

“So I do wonder, are we really helping these patients by transplanting them?” she added. “Similarly, the low-risk patients had a median time to treatment failure of 6 years; I wonder if they didn’t need a transplant.”

Biology

Ki-67 protein, a cellular marker for proliferation, is another important prognostic factor. A European Mantle Cell network study showed that median overall survival for patients with a Ki-67 proliferation index of less than 30% was not reached, and 5-year survival was 75%. At the same time, the median overall survival (OS) for those with Ki-67 proliferation index of 30% or greater was just 3.4 years, and 5-year OS was only 41% (J Clin Oncol. 2016 Apr 20;34[12]:1386-94).

The prognostic effect was independent of induction treatment, Dr. Blum said.

Combining MIPI and the Ki-67 index (MIPI-C) provides further value in defining a very high-risk group; those with both high MIPI and high Ki-67 had a median overall survival of only 1.5 years, and those with both, but who were under age 65, had median OS of only 1.7 years.
 

Histology

Patients with blastoid MCL variants were shown in that same study to have median OS of about 2.8 years, compared with 8 years in those with nonblastoid variants. The 5-year OS and progression-free survival (PFS) for blastoid variants were 35% and 29%, respectively, and for nonblastoid variants were 68% and 44%, respectively.

“But when you look at this with respect to the Ki-67 – so those patients that were called nonblastoid, that had a high Ki-67 index – their median overall survival is still lower at 5 years,” she said, noting that median OS was not reached in blastic variant (low-Ki-67) patients. “So it seems like the prognostic effect of cytology is largely explained by the Ki-67 index.”

In terms of karyotype, several studies have shown that complex karyotype is associated with poorer outcomes. One recent multicenter study of 274 patients showed that median OS in 53 patients with at least three cytogenetic abnormalities versus the remaining patients was 4.5 years vs. 11.6 years, and median PFS was 1.9 vs. 4.4 years (Cancer. 2018 Jun 1;124[11]:2306-15).

TP53 deletions (which affect about 20% of MCL patients) and mutations (which affect about 10%), are also useful prognostic factors, she said, noting that each is associated with inferior outcomes, and in one study patients with both appeared to have the worst outcomes (Blood. 2017;130:1903-10).

Another study showed that high TP53 staining (greater than 50% positive) is also associated with inferior outcomes, including reduced time to treatment failure and lower overall survival (Blood. 2018;131:417-20).

Finally, the most important factor is the patient’s wishes, Dr. Blum said, noting that she has “a lot of long discussions with these patients.”

“I consider all of these factors with each patient that I see with mantle cell,” she said.

Dr. Blum is a consultant for Acerta, AstraZeneca, and Molecular Templates and has received research funding from Acerta, AstraZeneca, Celgene, Cephalon, Immunomedics, Janssen, Merck, Millennium, Molecular Templates, Novartis, Pharmacyclics, and Seattle Genetics.

[email protected]

CHICAGO – The treatment options for patients with mantle cell lymphoma (MCL) vary based on age, but several prognostic factors can help guide treatment decision making in all patients, according to Kristie A. Blum, MD.

These include age, disease stage, disease sites, Mantle Cell Lymphoma International Prognostic Index (MIPI), biologic factors, and histology, Dr. Blum said during a presentation at the American Society of Hematology Meeting on Hematologic Malignancies.

Age

“I think the most important thing to recognize is there really isn’t any randomized transplant data for patients that are over 65. … There are very few transplant studies for patients [aged] 66-70,” said Dr. Blum, acting professor of hematology and medical oncology at Emory University in Atlanta.

The SWOG 0213 study did examine rituximab-hyperCVAD (R-HCVAD) in this age group, and showed that it has higher toxicity and lower efficacy in older versus younger patients, she said.

“Of course this is not typically a transplant approach, but an intensive-therapy approach,” she said, noting that progression-free and overall survival in patients aged 66-70 years were just 29% and 57%, respectively (Ann Oncol. 2013 Jun; 24[6]:1587-93).

Stage

Like age, disease stage in MCL patients has not been well studied, Dr. Blum said.

“Most of the randomized transplant studies have been conducted in patients stage II-IV, so we don’t have a lot of data about the early-stage patients,” she said, adding, however, that there are some retrospective data on radiation therapy for stage I-II MCL in older adults.

An International Lymphoma Radiation Oncology Group study of 179 patients, for example, showed that overall survival was “really the same whether they got chemo, chemo plus radiation, or radiation alone,” she said.

The 10-year freedom from progression was 46%, 43%, and 31%, respectively (P = .64).
 

Location

“What about where the disease presents? We’ve all heard about indolent mantle cell – so there’s this leukemic ‘non-nodal’ variant that’s been described,” she said, noting that this variant has a chronic lymphocytic leukemia–like presentation (no nodal disease, blood and marrow involvement, and splenic involvement). “And they tend to be SOX11-negative with mutated [immunoglobulin variable region heavy chain gene].”

Another variant involves primarily nodal disease that typically presents without elevated white blood cell count, with low Ki-67 (10% or lower), with SOX11 positivity, and without TP53 mutations.

“But I would caution you that this is really not very well defined; there’s no clear marker that predicts for indolent disease,” Dr. Blum said. “If you have one of these patients and you’re thinking about observing them, my experience has been that the most important thing to do is make sure you look at their [gastrointestinal] tract. I’ve had a lot of these patients progress with colon masses over time.”
 

MIPI

MIPI is basically a risk score calculated based on age, performance status, lactate dehydrogenase levels, and white cell count, she said.

MIPI less than 5.70 indicates low risk, MIPI of 5.70-6.2 is considered intermediate risk, and MIPI greater than 6.2 is considered high risk. High-risk patients who were transplanted in one study had a median overall survival of about 2.8 years and a median time to treatment failure of 1.4 years (J Clin Oncol. 2014 May 1;32[13]:1338-46). Even among patients under age 65 with high risk, the median time to treatment failure was 2 years, she said.

“So I do wonder, are we really helping these patients by transplanting them?” she added. “Similarly, the low-risk patients had a median time to treatment failure of 6 years; I wonder if they didn’t need a transplant.”

Biology

Ki-67 protein, a cellular marker for proliferation, is another important prognostic factor. A European Mantle Cell network study showed that median overall survival for patients with a Ki-67 proliferation index of less than 30% was not reached, and 5-year survival was 75%. At the same time, the median overall survival (OS) for those with Ki-67 proliferation index of 30% or greater was just 3.4 years, and 5-year OS was only 41% (J Clin Oncol. 2016 Apr 20;34[12]:1386-94).

The prognostic effect was independent of induction treatment, Dr. Blum said.

Combining MIPI and the Ki-67 index (MIPI-C) provides further value in defining a very high-risk group; those with both high MIPI and high Ki-67 had a median overall survival of only 1.5 years, and those with both, but who were under age 65, had median OS of only 1.7 years.
 

Histology

Patients with blastoid MCL variants were shown in that same study to have median OS of about 2.8 years, compared with 8 years in those with nonblastoid variants. The 5-year OS and progression-free survival (PFS) for blastoid variants were 35% and 29%, respectively, and for nonblastoid variants were 68% and 44%, respectively.

“But when you look at this with respect to the Ki-67 – so those patients that were called nonblastoid, that had a high Ki-67 index – their median overall survival is still lower at 5 years,” she said, noting that median OS was not reached in blastic variant (low-Ki-67) patients. “So it seems like the prognostic effect of cytology is largely explained by the Ki-67 index.”

In terms of karyotype, several studies have shown that complex karyotype is associated with poorer outcomes. One recent multicenter study of 274 patients showed that median OS in 53 patients with at least three cytogenetic abnormalities versus the remaining patients was 4.5 years vs. 11.6 years, and median PFS was 1.9 vs. 4.4 years (Cancer. 2018 Jun 1;124[11]:2306-15).

TP53 deletions (which affect about 20% of MCL patients) and mutations (which affect about 10%), are also useful prognostic factors, she said, noting that each is associated with inferior outcomes, and in one study patients with both appeared to have the worst outcomes (Blood. 2017;130:1903-10).

Another study showed that high TP53 staining (greater than 50% positive) is also associated with inferior outcomes, including reduced time to treatment failure and lower overall survival (Blood. 2018;131:417-20).

Finally, the most important factor is the patient’s wishes, Dr. Blum said, noting that she has “a lot of long discussions with these patients.”

“I consider all of these factors with each patient that I see with mantle cell,” she said.

Dr. Blum is a consultant for Acerta, AstraZeneca, and Molecular Templates and has received research funding from Acerta, AstraZeneca, Celgene, Cephalon, Immunomedics, Janssen, Merck, Millennium, Molecular Templates, Novartis, Pharmacyclics, and Seattle Genetics.

[email protected]

After 5 years, the combination of lenalidomide and rituximab as first-line therapy for mantle cell lymphoma (MCL) continues to show durable responses with manageable toxicities, long-term results from a phase 2 clinical trial show.

After a median follow-up of 64 months, 21 of 33 patients with initial responses remained in durable, minimal residual disease (MRD)-negative remission following induction with lenalidomide and rituximab and maintenance with those same two agents for at least 3 years.

The patients with durable responses included five who opted to discontinue maintenance after 3 years, reported Jia Ruan, MD, PhD, of Cornell University, New York, and her colleagues.

“Our long-term data provide proof of concept that an outpatient-based induction and maintenance strategy free of conventional chemotherapy is effective, safe, and feasible as first-line therapy for MCL,” they wrote. Their report was published in Blood.

In the multicenter, phase 2 single-arm study, 38 patients with untreated MCL were enrolled and treated with lenalidomide 20 mg daily on days 1-21 of each 28-day cycle for 12 cycles during induction, followed by dose reduction to 15 mg during the maintenance phase. Patients also received standard dose rituximab 375 mg/m² weekly for 4 weeks during cycle 1, then once every other cycle.

Patients remained on treatment until disease progression, unacceptable toxicities, or study withdrawal. Patients who remained in remission after 3 years, based on routine surveillance CT scans, had the option to discontinue maintenance.

Of the original 38 patients enrolled, 36 were evaluable for response, including 23 with a complete response (CR) and 10 with a partial response.

At the 64-month median follow-up, neither the median progression-free survival (PFS) nor duration of response had been reached.

Overall, 21 of the 33 patients with responses (64%) had ongoing responses, including six patients with responses beyond 6 years.

Estimated 3-year and 5-year PFS rates were 80.3% and 63.9%, respectively. Respective estimated 3- and 5-year overall survival rates were 89.5% and 77.4%.

Mantle cell lymphoma international prognostic index (MIPI) scores were not associated with either response or PFS rates, but patients with high-risk MIPI scores were significantly more likely to have worse overall survival (P = .04).

Grade 3 or greater hematologic toxicities included neutropenia in 42% of patients in both induction and maintenance, anemia in 8% and 3%, thrombocytopenia in 11% and 5%, and febrile neutropenia in 3% and 5%.

Secondary primary malignancies occurred in six patients. These included five noninvasive skin cancers requiring only local therapy without the need for study interruption. Two patients, including one with a skin cancer, died from the secondary malignancies, including one from Merkel cell carcinoma and one from pancreatic cancer.

“The efficacy and survival outcome observed in our study compared favorably to those reported with lenalidomide either as single agent, or in combination with rituximab in relapsed and refractory setting, lending support for prioritizing novel agents such as lenalidomide early in the treatment sequence, to compare to conventional chemotherapy-based approach,” the investigators wrote.

The study was supported in part by Celgene Corporation, a Clinical Translational Science Center grant, and the Lymphoma Foundation. Dr. Ruan has received research support and been a consultant for Celgene, and other coauthors reported research support and consultant relationships with the company.

SOURCE: Ruan J et al. Blood. 2018 Sep 4. doi: 10.1182/blood-2018-07-859769.

After 5 years, the combination of lenalidomide and rituximab as first-line therapy for mantle cell lymphoma (MCL) continues to show durable responses with manageable toxicities, long-term results from a phase 2 clinical trial show.

After a median follow-up of 64 months, 21 of 33 patients with initial responses remained in durable, minimal residual disease (MRD)-negative remission following induction with lenalidomide and rituximab and maintenance with those same two agents for at least 3 years.

The patients with durable responses included five who opted to discontinue maintenance after 3 years, reported Jia Ruan, MD, PhD, of Cornell University, New York, and her colleagues.

“Our long-term data provide proof of concept that an outpatient-based induction and maintenance strategy free of conventional chemotherapy is effective, safe, and feasible as first-line therapy for MCL,” they wrote. Their report was published in Blood.

In the multicenter, phase 2 single-arm study, 38 patients with untreated MCL were enrolled and treated with lenalidomide 20 mg daily on days 1-21 of each 28-day cycle for 12 cycles during induction, followed by dose reduction to 15 mg during the maintenance phase. Patients also received standard dose rituximab 375 mg/m² weekly for 4 weeks during cycle 1, then once every other cycle.

Patients remained on treatment until disease progression, unacceptable toxicities, or study withdrawal. Patients who remained in remission after 3 years, based on routine surveillance CT scans, had the option to discontinue maintenance.

Of the original 38 patients enrolled, 36 were evaluable for response, including 23 with a complete response (CR) and 10 with a partial response.

At the 64-month median follow-up, neither the median progression-free survival (PFS) nor duration of response had been reached.

Overall, 21 of the 33 patients with responses (64%) had ongoing responses, including six patients with responses beyond 6 years.

Estimated 3-year and 5-year PFS rates were 80.3% and 63.9%, respectively. Respective estimated 3- and 5-year overall survival rates were 89.5% and 77.4%.

Mantle cell lymphoma international prognostic index (MIPI) scores were not associated with either response or PFS rates, but patients with high-risk MIPI scores were significantly more likely to have worse overall survival (P = .04).

Grade 3 or greater hematologic toxicities included neutropenia in 42% of patients in both induction and maintenance, anemia in 8% and 3%, thrombocytopenia in 11% and 5%, and febrile neutropenia in 3% and 5%.

Secondary primary malignancies occurred in six patients. These included five noninvasive skin cancers requiring only local therapy without the need for study interruption. Two patients, including one with a skin cancer, died from the secondary malignancies, including one from Merkel cell carcinoma and one from pancreatic cancer.

“The efficacy and survival outcome observed in our study compared favorably to those reported with lenalidomide either as single agent, or in combination with rituximab in relapsed and refractory setting, lending support for prioritizing novel agents such as lenalidomide early in the treatment sequence, to compare to conventional chemotherapy-based approach,” the investigators wrote.

The study was supported in part by Celgene Corporation, a Clinical Translational Science Center grant, and the Lymphoma Foundation. Dr. Ruan has received research support and been a consultant for Celgene, and other coauthors reported research support and consultant relationships with the company.

SOURCE: Ruan J et al. Blood. 2018 Sep 4. doi: 10.1182/blood-2018-07-859769.

After 5 years, the combination of lenalidomide and rituximab as first-line therapy for mantle cell lymphoma (MCL) continues to show durable responses with manageable toxicities, long-term results from a phase 2 clinical trial show.

After a median follow-up of 64 months, 21 of 33 patients with initial responses remained in durable, minimal residual disease (MRD)-negative remission following induction with lenalidomide and rituximab and maintenance with those same two agents for at least 3 years.

The patients with durable responses included five who opted to discontinue maintenance after 3 years, reported Jia Ruan, MD, PhD, of Cornell University, New York, and her colleagues.

“Our long-term data provide proof of concept that an outpatient-based induction and maintenance strategy free of conventional chemotherapy is effective, safe, and feasible as first-line therapy for MCL,” they wrote. Their report was published in Blood.

In the multicenter, phase 2 single-arm study, 38 patients with untreated MCL were enrolled and treated with lenalidomide 20 mg daily on days 1-21 of each 28-day cycle for 12 cycles during induction, followed by dose reduction to 15 mg during the maintenance phase. Patients also received standard dose rituximab 375 mg/m² weekly for 4 weeks during cycle 1, then once every other cycle.

Patients remained on treatment until disease progression, unacceptable toxicities, or study withdrawal. Patients who remained in remission after 3 years, based on routine surveillance CT scans, had the option to discontinue maintenance.

Of the original 38 patients enrolled, 36 were evaluable for response, including 23 with a complete response (CR) and 10 with a partial response.

At the 64-month median follow-up, neither the median progression-free survival (PFS) nor duration of response had been reached.

Overall, 21 of the 33 patients with responses (64%) had ongoing responses, including six patients with responses beyond 6 years.

Estimated 3-year and 5-year PFS rates were 80.3% and 63.9%, respectively. Respective estimated 3- and 5-year overall survival rates were 89.5% and 77.4%.

Mantle cell lymphoma international prognostic index (MIPI) scores were not associated with either response or PFS rates, but patients with high-risk MIPI scores were significantly more likely to have worse overall survival (P = .04).

Grade 3 or greater hematologic toxicities included neutropenia in 42% of patients in both induction and maintenance, anemia in 8% and 3%, thrombocytopenia in 11% and 5%, and febrile neutropenia in 3% and 5%.

Secondary primary malignancies occurred in six patients. These included five noninvasive skin cancers requiring only local therapy without the need for study interruption. Two patients, including one with a skin cancer, died from the secondary malignancies, including one from Merkel cell carcinoma and one from pancreatic cancer.

“The efficacy and survival outcome observed in our study compared favorably to those reported with lenalidomide either as single agent, or in combination with rituximab in relapsed and refractory setting, lending support for prioritizing novel agents such as lenalidomide early in the treatment sequence, to compare to conventional chemotherapy-based approach,” the investigators wrote.

The study was supported in part by Celgene Corporation, a Clinical Translational Science Center grant, and the Lymphoma Foundation. Dr. Ruan has received research support and been a consultant for Celgene, and other coauthors reported research support and consultant relationships with the company.

SOURCE: Ruan J et al. Blood. 2018 Sep 4. doi: 10.1182/blood-2018-07-859769.

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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