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Early data support R-BAC for post-BTKi mantle cell lymphoma
GLASGOW – Patients with relapsed or refractory mantle cell lymphoma (MCL) who experience disease progression on a Bruton’s tyrosine kinase inhibitor (BTKi) may respond best to a combination of rituximab, bendamustine, and cytarabine (R-BAC), based on early results from an ongoing retrospective study.
Findings from the study, which were presented at the annual meeting of the British Society for Haematology, showed that R-BAC after BTKi failure had an overall response rate (ORR) of 90.5%.
This is a “remarkable response rate” according to the investigators, who cited previously reported response rates for other treatments ranging from 29% to 53%.
Treatment of relapsed/refractory MCL patients in the post-BTKi setting is an area of unmet clinical need, said senior author Simon Rule, MD, of the University of Plymouth, England. He noted that there is currently no consensus regarding best treatment strategy for this patient population.
Dr. Rule said that he and his colleagues have collected data on 30 patients so far, of which 22 were included in this early data release.
All patients received R-BAC between 2016 and 2018 at treatment centers in Italy and the United Kingdom. Treatment consisted of rituximab (375 mg/m2 or 500 mg) on day 1, bendamustine 70 mg/m2 on days 1 and 2, and cytarabine 500 mg/m2 on days 1 through 3, given in a 28-day cycle.
Patients received R-BAC immediately after BTKi failure. Data were drawn from hospital records.
Analysis showed that the median patient age was 65 years, with a range from 43 to 79 years. Most patients were men (81.8%), 55.0% were high risk based on the Mantle Cell Lymphoma International Prognostic Index, and 22.7% had blastoid morphology.
Patients had a median of two prior systemic therapies, with a range from one to six lines. First-line therapies included rituximab in combination with HDAC (high-dose cytarabine containing regimen), CHOP, CVP, or ibrutinib. Nine patients (42.9%) had allogeneic stem cell transplantation (ASCT) after induction treatment.
For BTKi therapy, most patients received ibrutinib (n = 18), while the remainder received acalabrutinib, tirabrutinib or M7583. Most patients discontinued BTKi therapy because of disease progression (90.9%); two patients stopped because of a lack of response (9.1%).
The median number of R-BAC cycles received was four. Two patients started with attenuated doses and seven patients reduced doses after the first cycle. More than 70% of patients completed R-BAC treatment.
The estimated median progression-free survival was 7.3 months and estimated median overall survival was 11.2 months.
Although the investigators reported a complete response rate of 57.1%, they noted that this figure “may be exaggerated” because of a lack of bone marrow biopsy; however, they suggested that the overall response rate (90.5%) “should be accurate.”
During the course of treatment, 31.8% of patients required inpatient admission, 22.7% developed neutropenic fever, and 77.8% required transfusion support. No treatment-related deaths occurred.
“This population, enriched for patients with high risk features, showed remarkable response rates to R-BAC,” the investigators wrote. “The treatment had acceptable toxicity, maintained efficacy at attenuated doses, and was used successfully as a bridge to ASCT in over 20% of patients.”
The investigators suggested that R-BAC should be considered a new standard of care in the United Kingdom for bendamustine-naive patients who are unable to be enrolled in clinical trials. “The high response rate makes it particularly appealing for patients considered candidates for consolidation ASCT,” they wrote.
In an interview, Dr. Rule added perspective to these findings.
“There’s been an obsession with venetoclax, that that’s the answer, but it really isn’t,” Dr. Rule said. “So people are looking for a new drug. I guess what I do differently to most people is I use CHOP frontline rather than bendamustine. To me, that’s the best way of sequencing the therapies, whereas if you use [bendamustine and rituximab] up front, which a lot of people do, particularly in the [United] States, your R-BAC might not be so effective.”
However, Dr. Rule said that first-line therapies appear to have minimal impact on R-BAC efficacy. “Even if you’ve had bendamustine, even if you’ve had high-dose cytarabine, even if you’ve had an allogeneic stem cell transplant, [R-BAC] still works,” he said.
Where patients have issues with tolerability, Dr. Rule noted that dose reductions are possible without sacrificing efficacy.
He offered an example of such a scenario. “My oldest patient was about 80 with blastoid disease, relapsing,” Dr. Rule said. “After ibrutinib, I gave him just a single dose of bendamustine at 70 mg, a single dose of cytarabine at 500 mg, just 1 day, and he had that six times, probably 3 weeks apart. He’s been in complete remission for over a year.”
With data on 30 patients collected, Dr. Rule said that he and his colleagues plan to present more extensive findings at the European Hematology Association Congress, held June 13-16 in Amsterdam.
The investigators reported having no conflicts of interest.
GLASGOW – Patients with relapsed or refractory mantle cell lymphoma (MCL) who experience disease progression on a Bruton’s tyrosine kinase inhibitor (BTKi) may respond best to a combination of rituximab, bendamustine, and cytarabine (R-BAC), based on early results from an ongoing retrospective study.
Findings from the study, which were presented at the annual meeting of the British Society for Haematology, showed that R-BAC after BTKi failure had an overall response rate (ORR) of 90.5%.
This is a “remarkable response rate” according to the investigators, who cited previously reported response rates for other treatments ranging from 29% to 53%.
Treatment of relapsed/refractory MCL patients in the post-BTKi setting is an area of unmet clinical need, said senior author Simon Rule, MD, of the University of Plymouth, England. He noted that there is currently no consensus regarding best treatment strategy for this patient population.
Dr. Rule said that he and his colleagues have collected data on 30 patients so far, of which 22 were included in this early data release.
All patients received R-BAC between 2016 and 2018 at treatment centers in Italy and the United Kingdom. Treatment consisted of rituximab (375 mg/m2 or 500 mg) on day 1, bendamustine 70 mg/m2 on days 1 and 2, and cytarabine 500 mg/m2 on days 1 through 3, given in a 28-day cycle.
Patients received R-BAC immediately after BTKi failure. Data were drawn from hospital records.
Analysis showed that the median patient age was 65 years, with a range from 43 to 79 years. Most patients were men (81.8%), 55.0% were high risk based on the Mantle Cell Lymphoma International Prognostic Index, and 22.7% had blastoid morphology.
Patients had a median of two prior systemic therapies, with a range from one to six lines. First-line therapies included rituximab in combination with HDAC (high-dose cytarabine containing regimen), CHOP, CVP, or ibrutinib. Nine patients (42.9%) had allogeneic stem cell transplantation (ASCT) after induction treatment.
For BTKi therapy, most patients received ibrutinib (n = 18), while the remainder received acalabrutinib, tirabrutinib or M7583. Most patients discontinued BTKi therapy because of disease progression (90.9%); two patients stopped because of a lack of response (9.1%).
The median number of R-BAC cycles received was four. Two patients started with attenuated doses and seven patients reduced doses after the first cycle. More than 70% of patients completed R-BAC treatment.
The estimated median progression-free survival was 7.3 months and estimated median overall survival was 11.2 months.
Although the investigators reported a complete response rate of 57.1%, they noted that this figure “may be exaggerated” because of a lack of bone marrow biopsy; however, they suggested that the overall response rate (90.5%) “should be accurate.”
During the course of treatment, 31.8% of patients required inpatient admission, 22.7% developed neutropenic fever, and 77.8% required transfusion support. No treatment-related deaths occurred.
“This population, enriched for patients with high risk features, showed remarkable response rates to R-BAC,” the investigators wrote. “The treatment had acceptable toxicity, maintained efficacy at attenuated doses, and was used successfully as a bridge to ASCT in over 20% of patients.”
The investigators suggested that R-BAC should be considered a new standard of care in the United Kingdom for bendamustine-naive patients who are unable to be enrolled in clinical trials. “The high response rate makes it particularly appealing for patients considered candidates for consolidation ASCT,” they wrote.
In an interview, Dr. Rule added perspective to these findings.
“There’s been an obsession with venetoclax, that that’s the answer, but it really isn’t,” Dr. Rule said. “So people are looking for a new drug. I guess what I do differently to most people is I use CHOP frontline rather than bendamustine. To me, that’s the best way of sequencing the therapies, whereas if you use [bendamustine and rituximab] up front, which a lot of people do, particularly in the [United] States, your R-BAC might not be so effective.”
However, Dr. Rule said that first-line therapies appear to have minimal impact on R-BAC efficacy. “Even if you’ve had bendamustine, even if you’ve had high-dose cytarabine, even if you’ve had an allogeneic stem cell transplant, [R-BAC] still works,” he said.
Where patients have issues with tolerability, Dr. Rule noted that dose reductions are possible without sacrificing efficacy.
He offered an example of such a scenario. “My oldest patient was about 80 with blastoid disease, relapsing,” Dr. Rule said. “After ibrutinib, I gave him just a single dose of bendamustine at 70 mg, a single dose of cytarabine at 500 mg, just 1 day, and he had that six times, probably 3 weeks apart. He’s been in complete remission for over a year.”
With data on 30 patients collected, Dr. Rule said that he and his colleagues plan to present more extensive findings at the European Hematology Association Congress, held June 13-16 in Amsterdam.
The investigators reported having no conflicts of interest.
GLASGOW – Patients with relapsed or refractory mantle cell lymphoma (MCL) who experience disease progression on a Bruton’s tyrosine kinase inhibitor (BTKi) may respond best to a combination of rituximab, bendamustine, and cytarabine (R-BAC), based on early results from an ongoing retrospective study.
Findings from the study, which were presented at the annual meeting of the British Society for Haematology, showed that R-BAC after BTKi failure had an overall response rate (ORR) of 90.5%.
This is a “remarkable response rate” according to the investigators, who cited previously reported response rates for other treatments ranging from 29% to 53%.
Treatment of relapsed/refractory MCL patients in the post-BTKi setting is an area of unmet clinical need, said senior author Simon Rule, MD, of the University of Plymouth, England. He noted that there is currently no consensus regarding best treatment strategy for this patient population.
Dr. Rule said that he and his colleagues have collected data on 30 patients so far, of which 22 were included in this early data release.
All patients received R-BAC between 2016 and 2018 at treatment centers in Italy and the United Kingdom. Treatment consisted of rituximab (375 mg/m2 or 500 mg) on day 1, bendamustine 70 mg/m2 on days 1 and 2, and cytarabine 500 mg/m2 on days 1 through 3, given in a 28-day cycle.
Patients received R-BAC immediately after BTKi failure. Data were drawn from hospital records.
Analysis showed that the median patient age was 65 years, with a range from 43 to 79 years. Most patients were men (81.8%), 55.0% were high risk based on the Mantle Cell Lymphoma International Prognostic Index, and 22.7% had blastoid morphology.
Patients had a median of two prior systemic therapies, with a range from one to six lines. First-line therapies included rituximab in combination with HDAC (high-dose cytarabine containing regimen), CHOP, CVP, or ibrutinib. Nine patients (42.9%) had allogeneic stem cell transplantation (ASCT) after induction treatment.
For BTKi therapy, most patients received ibrutinib (n = 18), while the remainder received acalabrutinib, tirabrutinib or M7583. Most patients discontinued BTKi therapy because of disease progression (90.9%); two patients stopped because of a lack of response (9.1%).
The median number of R-BAC cycles received was four. Two patients started with attenuated doses and seven patients reduced doses after the first cycle. More than 70% of patients completed R-BAC treatment.
The estimated median progression-free survival was 7.3 months and estimated median overall survival was 11.2 months.
Although the investigators reported a complete response rate of 57.1%, they noted that this figure “may be exaggerated” because of a lack of bone marrow biopsy; however, they suggested that the overall response rate (90.5%) “should be accurate.”
During the course of treatment, 31.8% of patients required inpatient admission, 22.7% developed neutropenic fever, and 77.8% required transfusion support. No treatment-related deaths occurred.
“This population, enriched for patients with high risk features, showed remarkable response rates to R-BAC,” the investigators wrote. “The treatment had acceptable toxicity, maintained efficacy at attenuated doses, and was used successfully as a bridge to ASCT in over 20% of patients.”
The investigators suggested that R-BAC should be considered a new standard of care in the United Kingdom for bendamustine-naive patients who are unable to be enrolled in clinical trials. “The high response rate makes it particularly appealing for patients considered candidates for consolidation ASCT,” they wrote.
In an interview, Dr. Rule added perspective to these findings.
“There’s been an obsession with venetoclax, that that’s the answer, but it really isn’t,” Dr. Rule said. “So people are looking for a new drug. I guess what I do differently to most people is I use CHOP frontline rather than bendamustine. To me, that’s the best way of sequencing the therapies, whereas if you use [bendamustine and rituximab] up front, which a lot of people do, particularly in the [United] States, your R-BAC might not be so effective.”
However, Dr. Rule said that first-line therapies appear to have minimal impact on R-BAC efficacy. “Even if you’ve had bendamustine, even if you’ve had high-dose cytarabine, even if you’ve had an allogeneic stem cell transplant, [R-BAC] still works,” he said.
Where patients have issues with tolerability, Dr. Rule noted that dose reductions are possible without sacrificing efficacy.
He offered an example of such a scenario. “My oldest patient was about 80 with blastoid disease, relapsing,” Dr. Rule said. “After ibrutinib, I gave him just a single dose of bendamustine at 70 mg, a single dose of cytarabine at 500 mg, just 1 day, and he had that six times, probably 3 weeks apart. He’s been in complete remission for over a year.”
With data on 30 patients collected, Dr. Rule said that he and his colleagues plan to present more extensive findings at the European Hematology Association Congress, held June 13-16 in Amsterdam.
The investigators reported having no conflicts of interest.
REPORTING FROM BSH 2019
MCL survival rates improve with novel agents
Survival outcomes for patients with mantle cell lymphoma (MCL) substantially improved from 1995 to 2013, particularly for those with advanced-stage tumors, according to a retrospective analysis.
The median overall survival for the study period was 52 months and 57 months in two cancer databases.
“Over the past 20 years, many novel agents and treatment regimens have been developed to treat MCL,” Shuangshuang Fu, PhD, of the University of Texas, Houston, and her colleagues wrote in Cancer Epidemiology.
The researchers retrospectively studied population-based data from two separate databases: the national Surveillance, Epidemiology and End Results (SEER) database and the Texas Cancer Registry (TCR). They identified all adult patients who received a new diagnosis of MCL between Jan. 1, 1995, and Dec. 31, 2013.
A total of 9,610 patients were included in the study: 7,555 patients from SEER and 2,055 from the TCR. The team collected data related to MCL diagnosis, mortality, and other variables, including age at diagnosis, marital status, sex, and tumor stage.
In total, 76.2% and 61.6% of patients from the SEER and TCR databases, respectively, had an advanced-stage tumor.
Dr. Fu and her colleagues found that all-cause mortality rates in both groups were significantly reduced from 1995 to 2013 (SEER, P less than .001; TCR, P = .03).
In addition, the team reported that the median overall survival time for all patients in the SEER database was 52 months, and it was 57 months for the TCR database.
“MCL patients with [an] advanced stage tumor benefitted most from the introduction of newly developed regimens,” they added.
The researchers acknowledged that a key limitation of the study was the inability to assess treatment regimen–specific survival, which could only be estimated with these data.
“The findings of our study further confirmed the impact of novel agents on improved survival over time that was shown in other studies,” they wrote.
The study was supported by grant funding from the Cancer Prevention Research Institute of Texas and the National Institutes of Health. The researchers reported having no conflicts of interest.
SOURCE: Fu S et al. Cancer Epidemiol. 2019 Feb;58:89-97.
Survival outcomes for patients with mantle cell lymphoma (MCL) substantially improved from 1995 to 2013, particularly for those with advanced-stage tumors, according to a retrospective analysis.
The median overall survival for the study period was 52 months and 57 months in two cancer databases.
“Over the past 20 years, many novel agents and treatment regimens have been developed to treat MCL,” Shuangshuang Fu, PhD, of the University of Texas, Houston, and her colleagues wrote in Cancer Epidemiology.
The researchers retrospectively studied population-based data from two separate databases: the national Surveillance, Epidemiology and End Results (SEER) database and the Texas Cancer Registry (TCR). They identified all adult patients who received a new diagnosis of MCL between Jan. 1, 1995, and Dec. 31, 2013.
A total of 9,610 patients were included in the study: 7,555 patients from SEER and 2,055 from the TCR. The team collected data related to MCL diagnosis, mortality, and other variables, including age at diagnosis, marital status, sex, and tumor stage.
In total, 76.2% and 61.6% of patients from the SEER and TCR databases, respectively, had an advanced-stage tumor.
Dr. Fu and her colleagues found that all-cause mortality rates in both groups were significantly reduced from 1995 to 2013 (SEER, P less than .001; TCR, P = .03).
In addition, the team reported that the median overall survival time for all patients in the SEER database was 52 months, and it was 57 months for the TCR database.
“MCL patients with [an] advanced stage tumor benefitted most from the introduction of newly developed regimens,” they added.
The researchers acknowledged that a key limitation of the study was the inability to assess treatment regimen–specific survival, which could only be estimated with these data.
“The findings of our study further confirmed the impact of novel agents on improved survival over time that was shown in other studies,” they wrote.
The study was supported by grant funding from the Cancer Prevention Research Institute of Texas and the National Institutes of Health. The researchers reported having no conflicts of interest.
SOURCE: Fu S et al. Cancer Epidemiol. 2019 Feb;58:89-97.
Survival outcomes for patients with mantle cell lymphoma (MCL) substantially improved from 1995 to 2013, particularly for those with advanced-stage tumors, according to a retrospective analysis.
The median overall survival for the study period was 52 months and 57 months in two cancer databases.
“Over the past 20 years, many novel agents and treatment regimens have been developed to treat MCL,” Shuangshuang Fu, PhD, of the University of Texas, Houston, and her colleagues wrote in Cancer Epidemiology.
The researchers retrospectively studied population-based data from two separate databases: the national Surveillance, Epidemiology and End Results (SEER) database and the Texas Cancer Registry (TCR). They identified all adult patients who received a new diagnosis of MCL between Jan. 1, 1995, and Dec. 31, 2013.
A total of 9,610 patients were included in the study: 7,555 patients from SEER and 2,055 from the TCR. The team collected data related to MCL diagnosis, mortality, and other variables, including age at diagnosis, marital status, sex, and tumor stage.
In total, 76.2% and 61.6% of patients from the SEER and TCR databases, respectively, had an advanced-stage tumor.
Dr. Fu and her colleagues found that all-cause mortality rates in both groups were significantly reduced from 1995 to 2013 (SEER, P less than .001; TCR, P = .03).
In addition, the team reported that the median overall survival time for all patients in the SEER database was 52 months, and it was 57 months for the TCR database.
“MCL patients with [an] advanced stage tumor benefitted most from the introduction of newly developed regimens,” they added.
The researchers acknowledged that a key limitation of the study was the inability to assess treatment regimen–specific survival, which could only be estimated with these data.
“The findings of our study further confirmed the impact of novel agents on improved survival over time that was shown in other studies,” they wrote.
The study was supported by grant funding from the Cancer Prevention Research Institute of Texas and the National Institutes of Health. The researchers reported having no conflicts of interest.
SOURCE: Fu S et al. Cancer Epidemiol. 2019 Feb;58:89-97.
FROM CANCER EPIDEMIOLOGY
Worse survival seen among black patients with MCL
Black non-Hispanic patients with mantle cell lymphoma (MCL) have a lower rate of 5-year overall survival, compared with white non-Hispanic and Hispanic patients, according to a retrospective analysis of more than 18,000 cases.
However, black patients were also most likely to receive treatment at an academic center, which was an independent predictor of better survival, reported Nikesh N. Shah, MD, of Emory University, Atlanta, and his colleagues. This finding suggests that even academic centers still need to focus on overcoming demographic disparities.
“Racial and socioeconomic differences have been reported in many malignancies and certain lymphomas; however, few studies report on disparities in MCL,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia. “To our knowledge this is the first such study to assess racial and socioeconomic disparities in this disease.”
The investigators reviewed 18,120 patients with MCL diagnosed between 2004 and 2013; data were drawn from the National Cancer Database. The primary endpoint was overall survival from the time of diagnosis, with analyses conducted to assess various associations with race/ethnicity, facility type, clinical/tumor characteristics, cancer stage, insurance type, and other factors.
Results showed that Hispanic patients had the highest rate of overall survival, at 55.8%, followed by white patients, at 50.1%. Trailing behind these groups were black patients (46.8%) and patients of other races/ethnicities (46.0%).
Along with survival disparities, race/ethnicity was tied to certain clinical and treatment characteristics. Compared with white patients, black patients were more likely to experience B symptoms (28% vs. 25%) and have Medicaid or lack insurance (15% vs. 5%). Black and Hispanic patients were also less likely than white non-Hispanic patients to receive stem cell transplant (13% vs. 10% vs. 10%).
Although black patients were more likely than white patients to receive treatment at an academic center (51% vs. 38%), a factor independently associated with best survival among center types, whatever advantage provided apparently did not exceed disadvantages associated with race.
“We report inferior overall survival in black patients after accounting for socioeconomic status, as seen in other malignancies,” the investigators wrote. “Surprisingly, these patients were more likely to be treated at academic centers, which independently showed improved overall survival in multivariable analysis that controlled for age, disease stage, insurance status, and other socioeconomic factors.”
The researchers cited a number of steps that could help close the survival gap, including providing more comprehensive supportive care between physician visits and enrollment of patients from diverse racial background on clinical trials.
The study was funded by the National Institutes of Health. The researchers reported having no conflicts of interest.
SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Mar 11. doi: 10.1016/j.clml.2019.03.006.
Black non-Hispanic patients with mantle cell lymphoma (MCL) have a lower rate of 5-year overall survival, compared with white non-Hispanic and Hispanic patients, according to a retrospective analysis of more than 18,000 cases.
However, black patients were also most likely to receive treatment at an academic center, which was an independent predictor of better survival, reported Nikesh N. Shah, MD, of Emory University, Atlanta, and his colleagues. This finding suggests that even academic centers still need to focus on overcoming demographic disparities.
“Racial and socioeconomic differences have been reported in many malignancies and certain lymphomas; however, few studies report on disparities in MCL,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia. “To our knowledge this is the first such study to assess racial and socioeconomic disparities in this disease.”
The investigators reviewed 18,120 patients with MCL diagnosed between 2004 and 2013; data were drawn from the National Cancer Database. The primary endpoint was overall survival from the time of diagnosis, with analyses conducted to assess various associations with race/ethnicity, facility type, clinical/tumor characteristics, cancer stage, insurance type, and other factors.
Results showed that Hispanic patients had the highest rate of overall survival, at 55.8%, followed by white patients, at 50.1%. Trailing behind these groups were black patients (46.8%) and patients of other races/ethnicities (46.0%).
Along with survival disparities, race/ethnicity was tied to certain clinical and treatment characteristics. Compared with white patients, black patients were more likely to experience B symptoms (28% vs. 25%) and have Medicaid or lack insurance (15% vs. 5%). Black and Hispanic patients were also less likely than white non-Hispanic patients to receive stem cell transplant (13% vs. 10% vs. 10%).
Although black patients were more likely than white patients to receive treatment at an academic center (51% vs. 38%), a factor independently associated with best survival among center types, whatever advantage provided apparently did not exceed disadvantages associated with race.
“We report inferior overall survival in black patients after accounting for socioeconomic status, as seen in other malignancies,” the investigators wrote. “Surprisingly, these patients were more likely to be treated at academic centers, which independently showed improved overall survival in multivariable analysis that controlled for age, disease stage, insurance status, and other socioeconomic factors.”
The researchers cited a number of steps that could help close the survival gap, including providing more comprehensive supportive care between physician visits and enrollment of patients from diverse racial background on clinical trials.
The study was funded by the National Institutes of Health. The researchers reported having no conflicts of interest.
SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Mar 11. doi: 10.1016/j.clml.2019.03.006.
Black non-Hispanic patients with mantle cell lymphoma (MCL) have a lower rate of 5-year overall survival, compared with white non-Hispanic and Hispanic patients, according to a retrospective analysis of more than 18,000 cases.
However, black patients were also most likely to receive treatment at an academic center, which was an independent predictor of better survival, reported Nikesh N. Shah, MD, of Emory University, Atlanta, and his colleagues. This finding suggests that even academic centers still need to focus on overcoming demographic disparities.
“Racial and socioeconomic differences have been reported in many malignancies and certain lymphomas; however, few studies report on disparities in MCL,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia. “To our knowledge this is the first such study to assess racial and socioeconomic disparities in this disease.”
The investigators reviewed 18,120 patients with MCL diagnosed between 2004 and 2013; data were drawn from the National Cancer Database. The primary endpoint was overall survival from the time of diagnosis, with analyses conducted to assess various associations with race/ethnicity, facility type, clinical/tumor characteristics, cancer stage, insurance type, and other factors.
Results showed that Hispanic patients had the highest rate of overall survival, at 55.8%, followed by white patients, at 50.1%. Trailing behind these groups were black patients (46.8%) and patients of other races/ethnicities (46.0%).
Along with survival disparities, race/ethnicity was tied to certain clinical and treatment characteristics. Compared with white patients, black patients were more likely to experience B symptoms (28% vs. 25%) and have Medicaid or lack insurance (15% vs. 5%). Black and Hispanic patients were also less likely than white non-Hispanic patients to receive stem cell transplant (13% vs. 10% vs. 10%).
Although black patients were more likely than white patients to receive treatment at an academic center (51% vs. 38%), a factor independently associated with best survival among center types, whatever advantage provided apparently did not exceed disadvantages associated with race.
“We report inferior overall survival in black patients after accounting for socioeconomic status, as seen in other malignancies,” the investigators wrote. “Surprisingly, these patients were more likely to be treated at academic centers, which independently showed improved overall survival in multivariable analysis that controlled for age, disease stage, insurance status, and other socioeconomic factors.”
The researchers cited a number of steps that could help close the survival gap, including providing more comprehensive supportive care between physician visits and enrollment of patients from diverse racial background on clinical trials.
The study was funded by the National Institutes of Health. The researchers reported having no conflicts of interest.
SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Mar 11. doi: 10.1016/j.clml.2019.03.006.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Bendamustine-rituximab shines in frontline treatment of MCL, iNHL
Frontline treatment with patients in the BRIGHT study.
The bendamustine-rituximab (BR) regimen had superior 5-year progression-free survival rates, event-free survival, and duration of response, compared with either rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP). The follow-up study did not find a significant difference in overall survival, however.
While the cumulative evidence from BRIGHT and other studies supports BR as a first-line treatment option for patients with indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL), the lack of an overall survival benefit indicates that the sequence of BR and R-CHOP or R-CVP “may not be critical,” Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute in Nashville, and his colleagues wrote in the Journal of Clinical Oncology.
“[The] choice of regimen for the initial treatment of iNHL may be driven more by patient preferences regarding the differences in toxicity profile,” the researchers wrote.
Initial results from the BRIGHT study found that BR was noninferior to R-CHOP/R-CVP in terms of complete response rate (P = .0225 for noninferiority). The present study includes outcomes data for at least 5 years after completion of the study treatment.
For the entire study, the median follow-up was 65.0 months for patients in the BR group and 64.1 months for patients in the R-CHOP/R-CVP group. Overall, the intention-to-treat population included 224 patients receiving BR and 223 patients receiving R-CHOP and R-CVP.
The median time to progression was not reached in either treatment group. The 5-year progression-free survival (PFS) rates were 65.5% in the BR group and 55.8% in the R-CHOP/R-CVP group. The difference between these rates was significant, with a hazard ratio of 0.61 (95% confidence interval, 0.45-0.85; P = .0025).
Similarly, event-free survival was better in the BR group versus the R-CHOP/R-CVP group (HR, 0.63; 95% CI, 0.46-0.84; P = .0020). Duration of response also favored the BR treatment regimen (HR, 0.66; 95% CI, 0.47-0.92; P = .0134).
The long-term follow-up showed no significant difference in overall survival, with an HR of 1.15 for BR versus R-CHOP/R-CVP (95% CI, 0.72-1.84; P = .5461). Overall, there were 40 deaths in the BR treatment group and 32 deaths in the R-CHOP/R-CVP group.
Whether patients received maintenance rituximab did not affect the overall survival between groups. Similarly, there was no difference in overall survival by lymphoma type.
“Benefit from BR treatment did not translate to prolonged [overall survival], possibly because of the subsequent lines of therapy, including the use of BR in patients in the R-CHOP/R-CVP group,” the researchers wrote.
In terms of safety, the follow-up data showed no significant difference in early non–disease-related mortality between the treatment groups. However, the BRIGHT study showed higher rates of secondary malignancies in the BR group, compared with R-CHOP/R-CVP. That finding was not seen in the Study Group of Indolent Lymphomas Non-Hodgkin Lymphoma (StiL NHL) 1 trial, and the authors could not provide an explanation for the increase in their research.
This study was supported by Teva Pharmaceuticals. Dr. Flinn reported receiving institutional research funding from Teva and receiving institutional research funding from or serving as a consultant to several other companies.
SOURCE: Flinn IW et al. J Clin Oncol. 2019 Feb 27. doi: 10.1200/JCO.18.00605.
Frontline treatment with patients in the BRIGHT study.
The bendamustine-rituximab (BR) regimen had superior 5-year progression-free survival rates, event-free survival, and duration of response, compared with either rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP). The follow-up study did not find a significant difference in overall survival, however.
While the cumulative evidence from BRIGHT and other studies supports BR as a first-line treatment option for patients with indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL), the lack of an overall survival benefit indicates that the sequence of BR and R-CHOP or R-CVP “may not be critical,” Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute in Nashville, and his colleagues wrote in the Journal of Clinical Oncology.
“[The] choice of regimen for the initial treatment of iNHL may be driven more by patient preferences regarding the differences in toxicity profile,” the researchers wrote.
Initial results from the BRIGHT study found that BR was noninferior to R-CHOP/R-CVP in terms of complete response rate (P = .0225 for noninferiority). The present study includes outcomes data for at least 5 years after completion of the study treatment.
For the entire study, the median follow-up was 65.0 months for patients in the BR group and 64.1 months for patients in the R-CHOP/R-CVP group. Overall, the intention-to-treat population included 224 patients receiving BR and 223 patients receiving R-CHOP and R-CVP.
The median time to progression was not reached in either treatment group. The 5-year progression-free survival (PFS) rates were 65.5% in the BR group and 55.8% in the R-CHOP/R-CVP group. The difference between these rates was significant, with a hazard ratio of 0.61 (95% confidence interval, 0.45-0.85; P = .0025).
Similarly, event-free survival was better in the BR group versus the R-CHOP/R-CVP group (HR, 0.63; 95% CI, 0.46-0.84; P = .0020). Duration of response also favored the BR treatment regimen (HR, 0.66; 95% CI, 0.47-0.92; P = .0134).
The long-term follow-up showed no significant difference in overall survival, with an HR of 1.15 for BR versus R-CHOP/R-CVP (95% CI, 0.72-1.84; P = .5461). Overall, there were 40 deaths in the BR treatment group and 32 deaths in the R-CHOP/R-CVP group.
Whether patients received maintenance rituximab did not affect the overall survival between groups. Similarly, there was no difference in overall survival by lymphoma type.
“Benefit from BR treatment did not translate to prolonged [overall survival], possibly because of the subsequent lines of therapy, including the use of BR in patients in the R-CHOP/R-CVP group,” the researchers wrote.
In terms of safety, the follow-up data showed no significant difference in early non–disease-related mortality between the treatment groups. However, the BRIGHT study showed higher rates of secondary malignancies in the BR group, compared with R-CHOP/R-CVP. That finding was not seen in the Study Group of Indolent Lymphomas Non-Hodgkin Lymphoma (StiL NHL) 1 trial, and the authors could not provide an explanation for the increase in their research.
This study was supported by Teva Pharmaceuticals. Dr. Flinn reported receiving institutional research funding from Teva and receiving institutional research funding from or serving as a consultant to several other companies.
SOURCE: Flinn IW et al. J Clin Oncol. 2019 Feb 27. doi: 10.1200/JCO.18.00605.
Frontline treatment with patients in the BRIGHT study.
The bendamustine-rituximab (BR) regimen had superior 5-year progression-free survival rates, event-free survival, and duration of response, compared with either rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP). The follow-up study did not find a significant difference in overall survival, however.
While the cumulative evidence from BRIGHT and other studies supports BR as a first-line treatment option for patients with indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL), the lack of an overall survival benefit indicates that the sequence of BR and R-CHOP or R-CVP “may not be critical,” Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute in Nashville, and his colleagues wrote in the Journal of Clinical Oncology.
“[The] choice of regimen for the initial treatment of iNHL may be driven more by patient preferences regarding the differences in toxicity profile,” the researchers wrote.
Initial results from the BRIGHT study found that BR was noninferior to R-CHOP/R-CVP in terms of complete response rate (P = .0225 for noninferiority). The present study includes outcomes data for at least 5 years after completion of the study treatment.
For the entire study, the median follow-up was 65.0 months for patients in the BR group and 64.1 months for patients in the R-CHOP/R-CVP group. Overall, the intention-to-treat population included 224 patients receiving BR and 223 patients receiving R-CHOP and R-CVP.
The median time to progression was not reached in either treatment group. The 5-year progression-free survival (PFS) rates were 65.5% in the BR group and 55.8% in the R-CHOP/R-CVP group. The difference between these rates was significant, with a hazard ratio of 0.61 (95% confidence interval, 0.45-0.85; P = .0025).
Similarly, event-free survival was better in the BR group versus the R-CHOP/R-CVP group (HR, 0.63; 95% CI, 0.46-0.84; P = .0020). Duration of response also favored the BR treatment regimen (HR, 0.66; 95% CI, 0.47-0.92; P = .0134).
The long-term follow-up showed no significant difference in overall survival, with an HR of 1.15 for BR versus R-CHOP/R-CVP (95% CI, 0.72-1.84; P = .5461). Overall, there were 40 deaths in the BR treatment group and 32 deaths in the R-CHOP/R-CVP group.
Whether patients received maintenance rituximab did not affect the overall survival between groups. Similarly, there was no difference in overall survival by lymphoma type.
“Benefit from BR treatment did not translate to prolonged [overall survival], possibly because of the subsequent lines of therapy, including the use of BR in patients in the R-CHOP/R-CVP group,” the researchers wrote.
In terms of safety, the follow-up data showed no significant difference in early non–disease-related mortality between the treatment groups. However, the BRIGHT study showed higher rates of secondary malignancies in the BR group, compared with R-CHOP/R-CVP. That finding was not seen in the Study Group of Indolent Lymphomas Non-Hodgkin Lymphoma (StiL NHL) 1 trial, and the authors could not provide an explanation for the increase in their research.
This study was supported by Teva Pharmaceuticals. Dr. Flinn reported receiving institutional research funding from Teva and receiving institutional research funding from or serving as a consultant to several other companies.
SOURCE: Flinn IW et al. J Clin Oncol. 2019 Feb 27. doi: 10.1200/JCO.18.00605.
FROM JOURNAL OF CLINICAL ONCOLOGY
Dual-targeted CAR T shows ‘clinical signal’ in NHL
HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.
The bispecific CAR T-cell product, designed to limit relapses due to loss of target antigen, was produced at the point of care with a 100% success rate for these heavily pretreated patients, the first of whom has now maintained a complete response for 19 months, said Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee.
“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.
“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.
There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.
Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 106 cells/kg, 5 remain in ongoing complete remission.
The median age of patients enrolled in the study was 55 years. Six patients had diffuse large B-cell lymphoma, five had mantle cell lymphoma, and two had chronic lymphocytic leukemia. All but one patient underwent fludarabine/cyclophosphamide lymphodepletion prior to receiving the inpatient CAR T-cell infusions, given over the course of 2 days.
Dr. Hari specifically highlighted the mantle cell lymphoma patient subset, noting that four out of five patients were in complete remission at day 28, and remained in ongoing complete remission at times ranging from 1 to 16 months.
With a set manufacturing time of 14 days, production was successful in all 12 patients, and 10 were able to receive fresh product, while 3 received cryopreserved product due to illness-related delays and a holiday, according to the investigators.
“The time to actual delivery of CAR T cell in the patient is actually shortened dramatically,” Dr. Hari said. “We hope to get it down to day 10.”
Local manufacturing can also reduce some costs associated with CAR T-cell production, such as shipping and courier costs, he added.
Taken together, these findings suggest that locally manufactured anti-CD19/CD20 CAR T cells could improve clinical outcomes for patients with relapsed and refractory B-cell NHL, with efficiency through point-of-care delivery, Dr. Hari concluded.
Further studies are planned to evaluate the efficacy of the product and to investigate the mechanism of relapse or progression in patients who experience treatment failure, he said.
Dr. Hari reported disclosures related to Juno, Kite, Spectrum, Janssen, Takeda, Celgene, and BMS. Several study coauthors reported that they were employed by Lentigen Technology, a Miltenyi Biotec Company.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Shah NN et al. TCT 2019, Abstract 80.
HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.
The bispecific CAR T-cell product, designed to limit relapses due to loss of target antigen, was produced at the point of care with a 100% success rate for these heavily pretreated patients, the first of whom has now maintained a complete response for 19 months, said Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee.
“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.
“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.
There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.
Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 106 cells/kg, 5 remain in ongoing complete remission.
The median age of patients enrolled in the study was 55 years. Six patients had diffuse large B-cell lymphoma, five had mantle cell lymphoma, and two had chronic lymphocytic leukemia. All but one patient underwent fludarabine/cyclophosphamide lymphodepletion prior to receiving the inpatient CAR T-cell infusions, given over the course of 2 days.
Dr. Hari specifically highlighted the mantle cell lymphoma patient subset, noting that four out of five patients were in complete remission at day 28, and remained in ongoing complete remission at times ranging from 1 to 16 months.
With a set manufacturing time of 14 days, production was successful in all 12 patients, and 10 were able to receive fresh product, while 3 received cryopreserved product due to illness-related delays and a holiday, according to the investigators.
“The time to actual delivery of CAR T cell in the patient is actually shortened dramatically,” Dr. Hari said. “We hope to get it down to day 10.”
Local manufacturing can also reduce some costs associated with CAR T-cell production, such as shipping and courier costs, he added.
Taken together, these findings suggest that locally manufactured anti-CD19/CD20 CAR T cells could improve clinical outcomes for patients with relapsed and refractory B-cell NHL, with efficiency through point-of-care delivery, Dr. Hari concluded.
Further studies are planned to evaluate the efficacy of the product and to investigate the mechanism of relapse or progression in patients who experience treatment failure, he said.
Dr. Hari reported disclosures related to Juno, Kite, Spectrum, Janssen, Takeda, Celgene, and BMS. Several study coauthors reported that they were employed by Lentigen Technology, a Miltenyi Biotec Company.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Shah NN et al. TCT 2019, Abstract 80.
HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.
The bispecific CAR T-cell product, designed to limit relapses due to loss of target antigen, was produced at the point of care with a 100% success rate for these heavily pretreated patients, the first of whom has now maintained a complete response for 19 months, said Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee.
“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.
“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.
There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.
Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 106 cells/kg, 5 remain in ongoing complete remission.
The median age of patients enrolled in the study was 55 years. Six patients had diffuse large B-cell lymphoma, five had mantle cell lymphoma, and two had chronic lymphocytic leukemia. All but one patient underwent fludarabine/cyclophosphamide lymphodepletion prior to receiving the inpatient CAR T-cell infusions, given over the course of 2 days.
Dr. Hari specifically highlighted the mantle cell lymphoma patient subset, noting that four out of five patients were in complete remission at day 28, and remained in ongoing complete remission at times ranging from 1 to 16 months.
With a set manufacturing time of 14 days, production was successful in all 12 patients, and 10 were able to receive fresh product, while 3 received cryopreserved product due to illness-related delays and a holiday, according to the investigators.
“The time to actual delivery of CAR T cell in the patient is actually shortened dramatically,” Dr. Hari said. “We hope to get it down to day 10.”
Local manufacturing can also reduce some costs associated with CAR T-cell production, such as shipping and courier costs, he added.
Taken together, these findings suggest that locally manufactured anti-CD19/CD20 CAR T cells could improve clinical outcomes for patients with relapsed and refractory B-cell NHL, with efficiency through point-of-care delivery, Dr. Hari concluded.
Further studies are planned to evaluate the efficacy of the product and to investigate the mechanism of relapse or progression in patients who experience treatment failure, he said.
Dr. Hari reported disclosures related to Juno, Kite, Spectrum, Janssen, Takeda, Celgene, and BMS. Several study coauthors reported that they were employed by Lentigen Technology, a Miltenyi Biotec Company.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Shah NN et al. TCT 2019, Abstract 80.
REPORTING FROM TCT 2019
Adding palbociclib upped responses in previously treated MCL
An early study adding palbociclib to ibrutinib in previously treated patients with mantle cell lymphoma (MCL) showed a higher complete response rate than what has previously been reported for single-agent ibrutinib, according to investigators.
Results from the phase 1 trial (NCT02159755) support preclinical models, suggesting that the CDK4/6 inhibitor palbociclib may be able to help overcome resistance to ibrutinib, an inhibitor of Bruton’s tyrosine kinase (BTK).
These findings set the stage for an ongoing phase 2 multicenter study, reported lead author Peter Martin, MD, of Weill Cornell Medicine in New York and his colleagues.
The present study involved 27 patients with previously treated MCL, the investigators wrote in Blood. Of these, 21 were men and 6 were women, all of whom had adequate organ and bone marrow function, good performance status, and no previous treatment with CDK4/6 or BTK inhibitors.
Patients were randomly grouped into five dose levels of each drug: Ibrutinib doses ranged from 280-560 mg, and palbociclib from 75-125 mg. Ibrutinib was given daily and palbociclib was administered for 21 out of 28 days per cycle. Therapy continued until withdrawal, unacceptable toxicity, or disease progression.
The primary objective was to determine phase 2 dose. Secondarily, the investigators sought to determine activity and toxicity profiles. The maximum tolerated doses were ibrutinib 560 mg daily plus palbociclib 100 mg on days 1-21 of each 28-day cycle.
Across all patients, the complete response rate was 37%, compared with 21% for ibrutinib monotherapy in a previous trial. About two-thirds of patients had a response of any kind, which aligns closely with the overall response rate previously reported for ibrutinib alone (67% vs. 68%). After a median follow-up of 25.6 months in survivors, the 2-year progression free survival was 59.4%. The two-year overall survival rate was 60.6%.
The dose-limiting toxicity was grade 3 rash, which occurred in two out of five patients treated at the highest doses. The most common grade 3 or higher toxicities were neutropenia (41%) and thrombocytopenia (30%), followed by hypertension (15%), febrile neutropenia (15%), lung infection (11%), fatigue (7%), upper respiratory tract infection (7%), hyperglycemia (7%), rash (7%), myalgia (7%), and increased alanine transaminase/aspartate aminotransferase (7%).
“Although BTK-inhibitor-based combinations appear promising, the degree to which they improve upon single-agent ibrutinib is unclear,” the investigators wrote, noting that a phase 2 trial (NCT03478514) is currently underway and uses the maximum tolerated doses.
The phase 1 trial was sponsored by the National Cancer Institute. Study funding was provided by the Sarah Cannon Fund at the HCA Foundation. The investigators reported financial relationships with Janssen, Gilead, AstraZeneca, Celgene, Karyopharm, and others.
SOURCE: Martin P et al. Blood. 2019 Jan 28. doi: 10.1182/blood-2018-11-886457.
An early study adding palbociclib to ibrutinib in previously treated patients with mantle cell lymphoma (MCL) showed a higher complete response rate than what has previously been reported for single-agent ibrutinib, according to investigators.
Results from the phase 1 trial (NCT02159755) support preclinical models, suggesting that the CDK4/6 inhibitor palbociclib may be able to help overcome resistance to ibrutinib, an inhibitor of Bruton’s tyrosine kinase (BTK).
These findings set the stage for an ongoing phase 2 multicenter study, reported lead author Peter Martin, MD, of Weill Cornell Medicine in New York and his colleagues.
The present study involved 27 patients with previously treated MCL, the investigators wrote in Blood. Of these, 21 were men and 6 were women, all of whom had adequate organ and bone marrow function, good performance status, and no previous treatment with CDK4/6 or BTK inhibitors.
Patients were randomly grouped into five dose levels of each drug: Ibrutinib doses ranged from 280-560 mg, and palbociclib from 75-125 mg. Ibrutinib was given daily and palbociclib was administered for 21 out of 28 days per cycle. Therapy continued until withdrawal, unacceptable toxicity, or disease progression.
The primary objective was to determine phase 2 dose. Secondarily, the investigators sought to determine activity and toxicity profiles. The maximum tolerated doses were ibrutinib 560 mg daily plus palbociclib 100 mg on days 1-21 of each 28-day cycle.
Across all patients, the complete response rate was 37%, compared with 21% for ibrutinib monotherapy in a previous trial. About two-thirds of patients had a response of any kind, which aligns closely with the overall response rate previously reported for ibrutinib alone (67% vs. 68%). After a median follow-up of 25.6 months in survivors, the 2-year progression free survival was 59.4%. The two-year overall survival rate was 60.6%.
The dose-limiting toxicity was grade 3 rash, which occurred in two out of five patients treated at the highest doses. The most common grade 3 or higher toxicities were neutropenia (41%) and thrombocytopenia (30%), followed by hypertension (15%), febrile neutropenia (15%), lung infection (11%), fatigue (7%), upper respiratory tract infection (7%), hyperglycemia (7%), rash (7%), myalgia (7%), and increased alanine transaminase/aspartate aminotransferase (7%).
“Although BTK-inhibitor-based combinations appear promising, the degree to which they improve upon single-agent ibrutinib is unclear,” the investigators wrote, noting that a phase 2 trial (NCT03478514) is currently underway and uses the maximum tolerated doses.
The phase 1 trial was sponsored by the National Cancer Institute. Study funding was provided by the Sarah Cannon Fund at the HCA Foundation. The investigators reported financial relationships with Janssen, Gilead, AstraZeneca, Celgene, Karyopharm, and others.
SOURCE: Martin P et al. Blood. 2019 Jan 28. doi: 10.1182/blood-2018-11-886457.
An early study adding palbociclib to ibrutinib in previously treated patients with mantle cell lymphoma (MCL) showed a higher complete response rate than what has previously been reported for single-agent ibrutinib, according to investigators.
Results from the phase 1 trial (NCT02159755) support preclinical models, suggesting that the CDK4/6 inhibitor palbociclib may be able to help overcome resistance to ibrutinib, an inhibitor of Bruton’s tyrosine kinase (BTK).
These findings set the stage for an ongoing phase 2 multicenter study, reported lead author Peter Martin, MD, of Weill Cornell Medicine in New York and his colleagues.
The present study involved 27 patients with previously treated MCL, the investigators wrote in Blood. Of these, 21 were men and 6 were women, all of whom had adequate organ and bone marrow function, good performance status, and no previous treatment with CDK4/6 or BTK inhibitors.
Patients were randomly grouped into five dose levels of each drug: Ibrutinib doses ranged from 280-560 mg, and palbociclib from 75-125 mg. Ibrutinib was given daily and palbociclib was administered for 21 out of 28 days per cycle. Therapy continued until withdrawal, unacceptable toxicity, or disease progression.
The primary objective was to determine phase 2 dose. Secondarily, the investigators sought to determine activity and toxicity profiles. The maximum tolerated doses were ibrutinib 560 mg daily plus palbociclib 100 mg on days 1-21 of each 28-day cycle.
Across all patients, the complete response rate was 37%, compared with 21% for ibrutinib monotherapy in a previous trial. About two-thirds of patients had a response of any kind, which aligns closely with the overall response rate previously reported for ibrutinib alone (67% vs. 68%). After a median follow-up of 25.6 months in survivors, the 2-year progression free survival was 59.4%. The two-year overall survival rate was 60.6%.
The dose-limiting toxicity was grade 3 rash, which occurred in two out of five patients treated at the highest doses. The most common grade 3 or higher toxicities were neutropenia (41%) and thrombocytopenia (30%), followed by hypertension (15%), febrile neutropenia (15%), lung infection (11%), fatigue (7%), upper respiratory tract infection (7%), hyperglycemia (7%), rash (7%), myalgia (7%), and increased alanine transaminase/aspartate aminotransferase (7%).
“Although BTK-inhibitor-based combinations appear promising, the degree to which they improve upon single-agent ibrutinib is unclear,” the investigators wrote, noting that a phase 2 trial (NCT03478514) is currently underway and uses the maximum tolerated doses.
The phase 1 trial was sponsored by the National Cancer Institute. Study funding was provided by the Sarah Cannon Fund at the HCA Foundation. The investigators reported financial relationships with Janssen, Gilead, AstraZeneca, Celgene, Karyopharm, and others.
SOURCE: Martin P et al. Blood. 2019 Jan 28. doi: 10.1182/blood-2018-11-886457.
FROM BLOOD
Key clinical point:
Major finding: The complete response rate for the combination treatment was 37%.
Study details: A prospective, phase 1 trial of 27 patients with previously treated MCL.
Disclosures: The trial was sponsored by the National Cancer Institute. Funding was provided by the Sarah Cannon Fund at the HCA Foundation. The investigators reported financial relationships with Janssen, Gilead, AstraZeneca, Celgene, Karyopharm, and others.
Source: Martin P et al. Blood. 2019 Jan 28. doi: 10.1182/blood-2018-11-886457.
Daratumumab disappoints in non-Hodgkin lymphoma trial
Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.
Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.
“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.
Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.
Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.
“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.
Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.
The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.
“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”
The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.
SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.
Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.
Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.
“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.
Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.
Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.
“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.
Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.
The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.
“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”
The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.
SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.
Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.
Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.
“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.
Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.
Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.
“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.
Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.
The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.
“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”
The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.
SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Key clinical point:
Major finding: The overall response rate was 12.5% for patients with follicular lymphoma and 6.7% for diffuse large B-cell lymphoma (DLBCL). There were no responders in the mantle cell lymphoma cohort.
Study details: An open-label, phase 2 trial involving 15 patients with diffuse large B-cell lymphoma, 16 patients with follicular lymphoma, and 5 patients with mantle cell lymphoma.
Disclosures: The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.
Source: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.
Combo appears to overcome aggressive L-NN-MCL
Some patients with aggressive leukemic nonnodal mantle cell lymphoma (L-NN-MCL) respond very well to combination therapy with rituximab and ibrutinib, according to two case reports.
Both patients, who had aggressive L-NN-MCL and P53 abnormalities, remain free of disease 18 months after treatment with rituximab/ibrutinib and autologous stem cell transplantation (ASCT), reported Shahram Mori, MD, PhD, of the Florida Hospital Cancer Institute in Orlando, and his colleagues.
The findings suggest that P53 gene status in L-NN-MCL may have a significant impact on prognosis and treatment planning. There are currently no guidelines for risk stratifying L-NN-MCL patients.
“Although the recognition of L-NN-MCL is important to avoid overtreatment, there appears to be a subset of patients who either have a more aggressive form or disease that has transformed to a more aggressive form who present with symptomatic disease and/or cytopenias,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.
The investigators described two such cases in their report. Both patients had leukocytosis with various other blood cell derangements and splenomegaly without lymphadenopathy.
The first patient was a 53-year-old African American man with L-NN-MCL and a number of genetic aberrations, including loss of the P53 gene. After two cycles of rituximab with bendamustine proved ineffective, he was switched to rituxan with cyclophosphamide, vincristine, adriamycin, and dexamethasone with high-dose methotrexate and cytarabine. This regimen was also ineffective and his white blood cell count kept rising.
His story changed for the better when the patient was switched to ibrutinib 560 mg daily and rituximab 375 mg/m2 monthly. Within 2 months of starting therapy, his blood abnormalities normalized, and bone marrow biopsy at the end of treatment revealed complete remission without evidence of minimal residual disease. The patient remains in complete remission 18 months after ASCT.
The second patient was a 49-year-old Hispanic man with L-NN-MCL. He had missense mutations in TP53 and KMT2A (MLL), a frameshift mutation in BCOR, and a t(11;14) translocation. Ibrutinib/rituximab was started immediately. After 1 month, his blood levels began to normalize. After five cycles, bone marrow biopsy showed complete remission with no evidence of minimal residual disease. Like the first patient, the second patient remains in complete remission 18 months after ASCT.
“To our knowledge, these are the first two cases of L-NN-MCL with P53 gene mutations/alterations that were successfully treated with a combination of rituximab and ibrutinib,” the investigators wrote. “Our two cases confirm the previous studies by Chapman-Fredricks et al, who also noted P53 gene mutation or deletion is associated with the aggressive course.”
The researchers reported having no financial disclosures.
SOURCE: Mori S et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):e93-7.
Some patients with aggressive leukemic nonnodal mantle cell lymphoma (L-NN-MCL) respond very well to combination therapy with rituximab and ibrutinib, according to two case reports.
Both patients, who had aggressive L-NN-MCL and P53 abnormalities, remain free of disease 18 months after treatment with rituximab/ibrutinib and autologous stem cell transplantation (ASCT), reported Shahram Mori, MD, PhD, of the Florida Hospital Cancer Institute in Orlando, and his colleagues.
The findings suggest that P53 gene status in L-NN-MCL may have a significant impact on prognosis and treatment planning. There are currently no guidelines for risk stratifying L-NN-MCL patients.
“Although the recognition of L-NN-MCL is important to avoid overtreatment, there appears to be a subset of patients who either have a more aggressive form or disease that has transformed to a more aggressive form who present with symptomatic disease and/or cytopenias,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.
The investigators described two such cases in their report. Both patients had leukocytosis with various other blood cell derangements and splenomegaly without lymphadenopathy.
The first patient was a 53-year-old African American man with L-NN-MCL and a number of genetic aberrations, including loss of the P53 gene. After two cycles of rituximab with bendamustine proved ineffective, he was switched to rituxan with cyclophosphamide, vincristine, adriamycin, and dexamethasone with high-dose methotrexate and cytarabine. This regimen was also ineffective and his white blood cell count kept rising.
His story changed for the better when the patient was switched to ibrutinib 560 mg daily and rituximab 375 mg/m2 monthly. Within 2 months of starting therapy, his blood abnormalities normalized, and bone marrow biopsy at the end of treatment revealed complete remission without evidence of minimal residual disease. The patient remains in complete remission 18 months after ASCT.
The second patient was a 49-year-old Hispanic man with L-NN-MCL. He had missense mutations in TP53 and KMT2A (MLL), a frameshift mutation in BCOR, and a t(11;14) translocation. Ibrutinib/rituximab was started immediately. After 1 month, his blood levels began to normalize. After five cycles, bone marrow biopsy showed complete remission with no evidence of minimal residual disease. Like the first patient, the second patient remains in complete remission 18 months after ASCT.
“To our knowledge, these are the first two cases of L-NN-MCL with P53 gene mutations/alterations that were successfully treated with a combination of rituximab and ibrutinib,” the investigators wrote. “Our two cases confirm the previous studies by Chapman-Fredricks et al, who also noted P53 gene mutation or deletion is associated with the aggressive course.”
The researchers reported having no financial disclosures.
SOURCE: Mori S et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):e93-7.
Some patients with aggressive leukemic nonnodal mantle cell lymphoma (L-NN-MCL) respond very well to combination therapy with rituximab and ibrutinib, according to two case reports.
Both patients, who had aggressive L-NN-MCL and P53 abnormalities, remain free of disease 18 months after treatment with rituximab/ibrutinib and autologous stem cell transplantation (ASCT), reported Shahram Mori, MD, PhD, of the Florida Hospital Cancer Institute in Orlando, and his colleagues.
The findings suggest that P53 gene status in L-NN-MCL may have a significant impact on prognosis and treatment planning. There are currently no guidelines for risk stratifying L-NN-MCL patients.
“Although the recognition of L-NN-MCL is important to avoid overtreatment, there appears to be a subset of patients who either have a more aggressive form or disease that has transformed to a more aggressive form who present with symptomatic disease and/or cytopenias,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.
The investigators described two such cases in their report. Both patients had leukocytosis with various other blood cell derangements and splenomegaly without lymphadenopathy.
The first patient was a 53-year-old African American man with L-NN-MCL and a number of genetic aberrations, including loss of the P53 gene. After two cycles of rituximab with bendamustine proved ineffective, he was switched to rituxan with cyclophosphamide, vincristine, adriamycin, and dexamethasone with high-dose methotrexate and cytarabine. This regimen was also ineffective and his white blood cell count kept rising.
His story changed for the better when the patient was switched to ibrutinib 560 mg daily and rituximab 375 mg/m2 monthly. Within 2 months of starting therapy, his blood abnormalities normalized, and bone marrow biopsy at the end of treatment revealed complete remission without evidence of minimal residual disease. The patient remains in complete remission 18 months after ASCT.
The second patient was a 49-year-old Hispanic man with L-NN-MCL. He had missense mutations in TP53 and KMT2A (MLL), a frameshift mutation in BCOR, and a t(11;14) translocation. Ibrutinib/rituximab was started immediately. After 1 month, his blood levels began to normalize. After five cycles, bone marrow biopsy showed complete remission with no evidence of minimal residual disease. Like the first patient, the second patient remains in complete remission 18 months after ASCT.
“To our knowledge, these are the first two cases of L-NN-MCL with P53 gene mutations/alterations that were successfully treated with a combination of rituximab and ibrutinib,” the investigators wrote. “Our two cases confirm the previous studies by Chapman-Fredricks et al, who also noted P53 gene mutation or deletion is associated with the aggressive course.”
The researchers reported having no financial disclosures.
SOURCE: Mori S et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):e93-7.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Key clinical point:
Major finding: Two patients with aggressive L-NN-MCL and P53 abnormalities who were treated with rituximab/ibrutinib and autologous stem cell transplantation remain free of disease 18 months later.
Study details: Two case reports.
Disclosures: The authors reported having no financial disclosures.
Source: Mori S et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):e93-7.
FDA grants BI-1206 orphan designation for MCL
The Food and Drug Administration has granted orphan designation to BI-1206 for the treatment of mantle cell lymphoma (MCL).
BI-1206 is a monoclonal antibody being developed by BioInvent International.
The company says BI-1206 works by inhibiting FcgRIIB (CD32B), which is associated with poor prognosis in MCL and other non-Hodgkin lymphomas. By inhibiting FcgRIIB, BI-1206 is expected to enhance the activity of rituximab or other anti-CD20 monoclonal antibodies.
BioInvent is conducting a phase 1/2a study (NCT03571568) of BI-1206 in combination with rituximab in patients with indolent, relapsed/refractory B-cell non-Hodgkin lymphomas, including MCL. The first patient began receiving treatment with BI-1206 in September 2018.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases or disorders that affect fewer than 200,000 people in the United States. Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The Food and Drug Administration has granted orphan designation to BI-1206 for the treatment of mantle cell lymphoma (MCL).
BI-1206 is a monoclonal antibody being developed by BioInvent International.
The company says BI-1206 works by inhibiting FcgRIIB (CD32B), which is associated with poor prognosis in MCL and other non-Hodgkin lymphomas. By inhibiting FcgRIIB, BI-1206 is expected to enhance the activity of rituximab or other anti-CD20 monoclonal antibodies.
BioInvent is conducting a phase 1/2a study (NCT03571568) of BI-1206 in combination with rituximab in patients with indolent, relapsed/refractory B-cell non-Hodgkin lymphomas, including MCL. The first patient began receiving treatment with BI-1206 in September 2018.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases or disorders that affect fewer than 200,000 people in the United States. Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The Food and Drug Administration has granted orphan designation to BI-1206 for the treatment of mantle cell lymphoma (MCL).
BI-1206 is a monoclonal antibody being developed by BioInvent International.
The company says BI-1206 works by inhibiting FcgRIIB (CD32B), which is associated with poor prognosis in MCL and other non-Hodgkin lymphomas. By inhibiting FcgRIIB, BI-1206 is expected to enhance the activity of rituximab or other anti-CD20 monoclonal antibodies.
BioInvent is conducting a phase 1/2a study (NCT03571568) of BI-1206 in combination with rituximab in patients with indolent, relapsed/refractory B-cell non-Hodgkin lymphomas, including MCL. The first patient began receiving treatment with BI-1206 in September 2018.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases or disorders that affect fewer than 200,000 people in the United States. Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
Autologous transplant linked to PFS benefit in MCL
Autologous hematopoietic cell transplantation (AHCT) was linked to improved progression-free survival, but not improved overall survival, in a retrospective cohort study including more than 1,000 mantle cell lymphoma (MCL) patients.
Use of consolidative AHCT was associated with improved progression-free survival even after the researchers controlled for disease severity in this cohort of younger, transplantation-eligible patients treated in the rituximab era, according to Stefan K. Barta, MD, of the University of Pennsylvania, Philadelphia, and his coinvestigators.
There was no such link between AHCT and improved overall survival in a propensity score–weighted analysis, though certain subgroups did seem to have an overall survival benefit, such as patients with high-risk features, Dr. Barta and his colleagues reported in the Journal of Clinical Oncology.
By contrast, other recent studies have found an association between consolidative AHCT and improved overall survival in MCL, including another recently reported retrospective analysis of 10,000 patients in the National Cancer Database.
The lack of overall survival improvement seen in the present study may be due to effective salvage therapy with novel agents or additional transplantation, abrogating any improvement that otherwise might be attributable to AHCT, Dr. Barta and his coauthors said in a discussion of their results.
The present analysis included 1,029 transplantation-eligible adults aged 65 years or younger with a new diagnosis of MCL, who were treated between 2000 and 2015 at one of 25 medical centers. About two-thirds of the patients underwent consolidative AHCT.
With a median follow-up of 76 months, median progression-free survival was 62 months, and median overall survival was 138 months, the investigators reported.
While AHCT was linked to improved progression-free survival and overall survival in an unadjusted analysis, subsequent analyses showed only a trend toward improvement or no improvement in overall survival.
Specifically, AHCT was associated with improved progression-free survival in multivariable regression analysis, with a hazard ratio (HR) of 0.53 (95% confidence interval, 0.43-0.66; P less than .01) and in propensity score–weighted analysis (HR, 0.70; 95% CI, 0.59-0.84; P less than .05).
By contrast, AHCT was associated with a trend toward improved overall survival in the multivariable analysis (HR, 0.77; 95% CI, 0.98 to 1.01; P = .06) and no improvement in overall survival in the propensity score–weighted analysis (HR, 0.87; 95% CI, 0.69 to 1.10; P = .24).
A subgroup analysis conducted after the multivariable analysis found that overall survival improvements were seen only in patients who received CHOP-like induction or induction without cytarabine, or those who had blastoid or pleomorphic variant or who scored high on the MCL International Prognostic Index.
Randomized trials are “urgently needed” to determine the true benefit of consolidative AHCT in MCL, Dr. Barta and his coauthors said, since some subgroups likely derive minimal benefit from it, including patients with TP53 mutations or those who are minimal residual disease (MRD) negative following induction.
One such study is EA4151, an ongoing randomized, phase 3 clinical trial, which is evaluating consolidation with AHCT followed by maintenance rituximab versus maintenance rituximab alone for MCL patients in MRD-negative first complete remission.
“With this and other well-designed prospective trials as well as with well-validated predictive biomarkers, clinicians will be better able to provide a more refined, risk-adapted approach to first-line management of MCL,” the investigators said.
Dr. Barta provided no disclosures related to the research. Coauthors had disclosures related to Sanofi, AstraZeneca, Celgene, Adaptive Biotechnologies, Janssen Oncology, Seattle Genetics, Genentech, Pharmacyclics, Merck, Bristol-Myers Squibb, and others.
SOURCE: Gerson JN et al. J Clin Oncol. 2019 Jan 7. doi: 10.1200/JCO.18.00690.
Autologous hematopoietic cell transplantation (AHCT) was linked to improved progression-free survival, but not improved overall survival, in a retrospective cohort study including more than 1,000 mantle cell lymphoma (MCL) patients.
Use of consolidative AHCT was associated with improved progression-free survival even after the researchers controlled for disease severity in this cohort of younger, transplantation-eligible patients treated in the rituximab era, according to Stefan K. Barta, MD, of the University of Pennsylvania, Philadelphia, and his coinvestigators.
There was no such link between AHCT and improved overall survival in a propensity score–weighted analysis, though certain subgroups did seem to have an overall survival benefit, such as patients with high-risk features, Dr. Barta and his colleagues reported in the Journal of Clinical Oncology.
By contrast, other recent studies have found an association between consolidative AHCT and improved overall survival in MCL, including another recently reported retrospective analysis of 10,000 patients in the National Cancer Database.
The lack of overall survival improvement seen in the present study may be due to effective salvage therapy with novel agents or additional transplantation, abrogating any improvement that otherwise might be attributable to AHCT, Dr. Barta and his coauthors said in a discussion of their results.
The present analysis included 1,029 transplantation-eligible adults aged 65 years or younger with a new diagnosis of MCL, who were treated between 2000 and 2015 at one of 25 medical centers. About two-thirds of the patients underwent consolidative AHCT.
With a median follow-up of 76 months, median progression-free survival was 62 months, and median overall survival was 138 months, the investigators reported.
While AHCT was linked to improved progression-free survival and overall survival in an unadjusted analysis, subsequent analyses showed only a trend toward improvement or no improvement in overall survival.
Specifically, AHCT was associated with improved progression-free survival in multivariable regression analysis, with a hazard ratio (HR) of 0.53 (95% confidence interval, 0.43-0.66; P less than .01) and in propensity score–weighted analysis (HR, 0.70; 95% CI, 0.59-0.84; P less than .05).
By contrast, AHCT was associated with a trend toward improved overall survival in the multivariable analysis (HR, 0.77; 95% CI, 0.98 to 1.01; P = .06) and no improvement in overall survival in the propensity score–weighted analysis (HR, 0.87; 95% CI, 0.69 to 1.10; P = .24).
A subgroup analysis conducted after the multivariable analysis found that overall survival improvements were seen only in patients who received CHOP-like induction or induction without cytarabine, or those who had blastoid or pleomorphic variant or who scored high on the MCL International Prognostic Index.
Randomized trials are “urgently needed” to determine the true benefit of consolidative AHCT in MCL, Dr. Barta and his coauthors said, since some subgroups likely derive minimal benefit from it, including patients with TP53 mutations or those who are minimal residual disease (MRD) negative following induction.
One such study is EA4151, an ongoing randomized, phase 3 clinical trial, which is evaluating consolidation with AHCT followed by maintenance rituximab versus maintenance rituximab alone for MCL patients in MRD-negative first complete remission.
“With this and other well-designed prospective trials as well as with well-validated predictive biomarkers, clinicians will be better able to provide a more refined, risk-adapted approach to first-line management of MCL,” the investigators said.
Dr. Barta provided no disclosures related to the research. Coauthors had disclosures related to Sanofi, AstraZeneca, Celgene, Adaptive Biotechnologies, Janssen Oncology, Seattle Genetics, Genentech, Pharmacyclics, Merck, Bristol-Myers Squibb, and others.
SOURCE: Gerson JN et al. J Clin Oncol. 2019 Jan 7. doi: 10.1200/JCO.18.00690.
Autologous hematopoietic cell transplantation (AHCT) was linked to improved progression-free survival, but not improved overall survival, in a retrospective cohort study including more than 1,000 mantle cell lymphoma (MCL) patients.
Use of consolidative AHCT was associated with improved progression-free survival even after the researchers controlled for disease severity in this cohort of younger, transplantation-eligible patients treated in the rituximab era, according to Stefan K. Barta, MD, of the University of Pennsylvania, Philadelphia, and his coinvestigators.
There was no such link between AHCT and improved overall survival in a propensity score–weighted analysis, though certain subgroups did seem to have an overall survival benefit, such as patients with high-risk features, Dr. Barta and his colleagues reported in the Journal of Clinical Oncology.
By contrast, other recent studies have found an association between consolidative AHCT and improved overall survival in MCL, including another recently reported retrospective analysis of 10,000 patients in the National Cancer Database.
The lack of overall survival improvement seen in the present study may be due to effective salvage therapy with novel agents or additional transplantation, abrogating any improvement that otherwise might be attributable to AHCT, Dr. Barta and his coauthors said in a discussion of their results.
The present analysis included 1,029 transplantation-eligible adults aged 65 years or younger with a new diagnosis of MCL, who were treated between 2000 and 2015 at one of 25 medical centers. About two-thirds of the patients underwent consolidative AHCT.
With a median follow-up of 76 months, median progression-free survival was 62 months, and median overall survival was 138 months, the investigators reported.
While AHCT was linked to improved progression-free survival and overall survival in an unadjusted analysis, subsequent analyses showed only a trend toward improvement or no improvement in overall survival.
Specifically, AHCT was associated with improved progression-free survival in multivariable regression analysis, with a hazard ratio (HR) of 0.53 (95% confidence interval, 0.43-0.66; P less than .01) and in propensity score–weighted analysis (HR, 0.70; 95% CI, 0.59-0.84; P less than .05).
By contrast, AHCT was associated with a trend toward improved overall survival in the multivariable analysis (HR, 0.77; 95% CI, 0.98 to 1.01; P = .06) and no improvement in overall survival in the propensity score–weighted analysis (HR, 0.87; 95% CI, 0.69 to 1.10; P = .24).
A subgroup analysis conducted after the multivariable analysis found that overall survival improvements were seen only in patients who received CHOP-like induction or induction without cytarabine, or those who had blastoid or pleomorphic variant or who scored high on the MCL International Prognostic Index.
Randomized trials are “urgently needed” to determine the true benefit of consolidative AHCT in MCL, Dr. Barta and his coauthors said, since some subgroups likely derive minimal benefit from it, including patients with TP53 mutations or those who are minimal residual disease (MRD) negative following induction.
One such study is EA4151, an ongoing randomized, phase 3 clinical trial, which is evaluating consolidation with AHCT followed by maintenance rituximab versus maintenance rituximab alone for MCL patients in MRD-negative first complete remission.
“With this and other well-designed prospective trials as well as with well-validated predictive biomarkers, clinicians will be better able to provide a more refined, risk-adapted approach to first-line management of MCL,” the investigators said.
Dr. Barta provided no disclosures related to the research. Coauthors had disclosures related to Sanofi, AstraZeneca, Celgene, Adaptive Biotechnologies, Janssen Oncology, Seattle Genetics, Genentech, Pharmacyclics, Merck, Bristol-Myers Squibb, and others.
SOURCE: Gerson JN et al. J Clin Oncol. 2019 Jan 7. doi: 10.1200/JCO.18.00690.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: AHCT was associated with improved progression-free survival in a propensity score–weighted analysis (hazard ratio, 0.70; P less than .05).
Study details: A retrospective cohort study including 1,029 transplantation-eligible adults aged 65 years or younger with newly diagnosed MCL.
Disclosures: The authors reported disclosures related to Sanofi, AstraZeneca, Celgene, Adaptive Biotechnologies, Janssen Oncology, Seattle Genetics, Genentech, Pharmacyclics, Merck, Bristol-Myers Squibb, and others.
Source: Gerson JN et al. J Clin Oncol. 2019 Jan 7. doi: 10.1200/JCO.18.00690.