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B-cell cancers: Sparse insight into preventing infections
Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.
Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.
The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.
As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.
“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”
The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).
No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.
Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).
Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.
No intervention reduced all-cause mortality.
“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”
The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”
More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.
What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”
He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”
In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”
Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”
As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”
Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”
Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.
Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.
Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.
The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.
As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.
“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”
The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).
No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.
Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).
Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.
No intervention reduced all-cause mortality.
“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”
The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”
More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.
What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”
He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”
In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”
Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”
As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”
Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”
Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.
Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.
Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.
The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.
As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.
“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”
The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).
No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.
Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).
Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.
No intervention reduced all-cause mortality.
“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”
The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”
More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.
What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”
He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”
In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”
Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”
As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”
Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”
Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.
FROM BLOOD ADVANCES
Standard first‐line chemotherapies for indolent B‐cell lymphoma impose varying risks for a second cancer
Key clinical point: The risk for a second primary malignancy (SPM) was higher in patients with indolent B‐cell lymphoma (iBCL) treated with bendamustine/rituximab (BR) vs rituximab monotherapy and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) or rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) or rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (RTHPCOP).
Major finding: The cumulative incidence of SPM was significantly higher among patients receiving BR vs rituximab monotherapy (P < .01) or RCHOP/RCVP/RTHPCOP (P < .0001). The 5‐year cumulative incidence rates with BR, rituximab monotherapy, and RCHOP/RCVP/RTHPCOP were 18.1%, 12.5%, and 12.9%, respectively.
Study details: This retrospective observational study included 5234 adult patients with iBCL who received rituximab monotherapy (n = 780), RCHOP/RCVP/RTHPCOP (n = 2298), or BR (n = 2156).
Disclosures: This study was supported by the Japan Society for the Promotion of Science. Y Muraki declared receiving a lecture honorarium from Pfizer Japan, Inc.
Source: Dote S et al. Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database. Hematol Oncol. 2023 (Feb 15). Doi: 10.1002/hon.3128.
Key clinical point: The risk for a second primary malignancy (SPM) was higher in patients with indolent B‐cell lymphoma (iBCL) treated with bendamustine/rituximab (BR) vs rituximab monotherapy and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) or rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) or rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (RTHPCOP).
Major finding: The cumulative incidence of SPM was significantly higher among patients receiving BR vs rituximab monotherapy (P < .01) or RCHOP/RCVP/RTHPCOP (P < .0001). The 5‐year cumulative incidence rates with BR, rituximab monotherapy, and RCHOP/RCVP/RTHPCOP were 18.1%, 12.5%, and 12.9%, respectively.
Study details: This retrospective observational study included 5234 adult patients with iBCL who received rituximab monotherapy (n = 780), RCHOP/RCVP/RTHPCOP (n = 2298), or BR (n = 2156).
Disclosures: This study was supported by the Japan Society for the Promotion of Science. Y Muraki declared receiving a lecture honorarium from Pfizer Japan, Inc.
Source: Dote S et al. Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database. Hematol Oncol. 2023 (Feb 15). Doi: 10.1002/hon.3128.
Key clinical point: The risk for a second primary malignancy (SPM) was higher in patients with indolent B‐cell lymphoma (iBCL) treated with bendamustine/rituximab (BR) vs rituximab monotherapy and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) or rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) or rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (RTHPCOP).
Major finding: The cumulative incidence of SPM was significantly higher among patients receiving BR vs rituximab monotherapy (P < .01) or RCHOP/RCVP/RTHPCOP (P < .0001). The 5‐year cumulative incidence rates with BR, rituximab monotherapy, and RCHOP/RCVP/RTHPCOP were 18.1%, 12.5%, and 12.9%, respectively.
Study details: This retrospective observational study included 5234 adult patients with iBCL who received rituximab monotherapy (n = 780), RCHOP/RCVP/RTHPCOP (n = 2298), or BR (n = 2156).
Disclosures: This study was supported by the Japan Society for the Promotion of Science. Y Muraki declared receiving a lecture honorarium from Pfizer Japan, Inc.
Source: Dote S et al. Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database. Hematol Oncol. 2023 (Feb 15). Doi: 10.1002/hon.3128.
High-dose total body irradiation followed by stem cell transplantation offers long-term survival in MCL
Key clinical point: Multimodal treatment comprising total body irradiation (TBI), high-dose chemotherapy, and autologous stem cell transplantation (autoSCT) offers long-term survival in patients with mantle cell lymphoma (MCL).
Major finding: The median overall survival of patients who underwent TBI and autoSCT was 11.4 years, whereas that of patients who underwent TBI and allogenic stem cell transplantation (alloSCT) was 3.25 years. Compared with the whole cohort, patients receiving autoSCT presented a better overall survival rate (50.0% vs 57.9%) after reaching a plateau at 6.8 years.
Study details: Findings are from a single-center retrospective study including 22 patients with advanced MCL who underwent TBI before autoSCT (n = 19) or alloSCT (n = 3).
Disclosures: This study received no external funding. The authors declared no conflict on interests.
Source: Kröger K et al. Long-term survival of patients with mantle cell lymphoma after total body irradiation, high-dose chemotherapy and stem cell transplantation: A monocenter study. Cancers (Basel). 2023;15(3):983 (Feb 3). Doi: 10.3390/cancers15030983
Key clinical point: Multimodal treatment comprising total body irradiation (TBI), high-dose chemotherapy, and autologous stem cell transplantation (autoSCT) offers long-term survival in patients with mantle cell lymphoma (MCL).
Major finding: The median overall survival of patients who underwent TBI and autoSCT was 11.4 years, whereas that of patients who underwent TBI and allogenic stem cell transplantation (alloSCT) was 3.25 years. Compared with the whole cohort, patients receiving autoSCT presented a better overall survival rate (50.0% vs 57.9%) after reaching a plateau at 6.8 years.
Study details: Findings are from a single-center retrospective study including 22 patients with advanced MCL who underwent TBI before autoSCT (n = 19) or alloSCT (n = 3).
Disclosures: This study received no external funding. The authors declared no conflict on interests.
Source: Kröger K et al. Long-term survival of patients with mantle cell lymphoma after total body irradiation, high-dose chemotherapy and stem cell transplantation: A monocenter study. Cancers (Basel). 2023;15(3):983 (Feb 3). Doi: 10.3390/cancers15030983
Key clinical point: Multimodal treatment comprising total body irradiation (TBI), high-dose chemotherapy, and autologous stem cell transplantation (autoSCT) offers long-term survival in patients with mantle cell lymphoma (MCL).
Major finding: The median overall survival of patients who underwent TBI and autoSCT was 11.4 years, whereas that of patients who underwent TBI and allogenic stem cell transplantation (alloSCT) was 3.25 years. Compared with the whole cohort, patients receiving autoSCT presented a better overall survival rate (50.0% vs 57.9%) after reaching a plateau at 6.8 years.
Study details: Findings are from a single-center retrospective study including 22 patients with advanced MCL who underwent TBI before autoSCT (n = 19) or alloSCT (n = 3).
Disclosures: This study received no external funding. The authors declared no conflict on interests.
Source: Kröger K et al. Long-term survival of patients with mantle cell lymphoma after total body irradiation, high-dose chemotherapy and stem cell transplantation: A monocenter study. Cancers (Basel). 2023;15(3):983 (Feb 3). Doi: 10.3390/cancers15030983
A complete assessment of TP53 aberrations recommended before initiating ibrutinib in CLL
Key clinical point: Only the copresence of TP53 deletion (del17p) and mutations and not a single aberration has a negative prognostic impact in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib treatment.
Major finding: Only patients with concomitant TP53 mutations and del17p had significantly shorter overall survival (OS; P = .0073) and progression-free survival (PFS; P = .0037) than those with no TP53 aberration; no difference in OS or PFS was observed in patients with single aberration. TP53 mutation and del17p copresence was an independent predictor for short OS and PFS (adjusted hazard ratio 2.27; P = .0077).
Study details: This multicenter retrospective study included 229 patients with CLL treated with ibrutinib who were assayed for TP53 mutation and del17p in the same blood sample that was collected within 6 months before initiating ibrutinib.
Disclosures: This study was supported in part by the Italian Ministry of Health “Progetto Ricerca Finalizzata” and others. The authors declared no conflicts of interest.
Source: Bomben R et al. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: A campus CLL study. Leukemia. 2023 (Feb 18). Doi: 10.1038/s41375-023-01845-9
Key clinical point: Only the copresence of TP53 deletion (del17p) and mutations and not a single aberration has a negative prognostic impact in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib treatment.
Major finding: Only patients with concomitant TP53 mutations and del17p had significantly shorter overall survival (OS; P = .0073) and progression-free survival (PFS; P = .0037) than those with no TP53 aberration; no difference in OS or PFS was observed in patients with single aberration. TP53 mutation and del17p copresence was an independent predictor for short OS and PFS (adjusted hazard ratio 2.27; P = .0077).
Study details: This multicenter retrospective study included 229 patients with CLL treated with ibrutinib who were assayed for TP53 mutation and del17p in the same blood sample that was collected within 6 months before initiating ibrutinib.
Disclosures: This study was supported in part by the Italian Ministry of Health “Progetto Ricerca Finalizzata” and others. The authors declared no conflicts of interest.
Source: Bomben R et al. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: A campus CLL study. Leukemia. 2023 (Feb 18). Doi: 10.1038/s41375-023-01845-9
Key clinical point: Only the copresence of TP53 deletion (del17p) and mutations and not a single aberration has a negative prognostic impact in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib treatment.
Major finding: Only patients with concomitant TP53 mutations and del17p had significantly shorter overall survival (OS; P = .0073) and progression-free survival (PFS; P = .0037) than those with no TP53 aberration; no difference in OS or PFS was observed in patients with single aberration. TP53 mutation and del17p copresence was an independent predictor for short OS and PFS (adjusted hazard ratio 2.27; P = .0077).
Study details: This multicenter retrospective study included 229 patients with CLL treated with ibrutinib who were assayed for TP53 mutation and del17p in the same blood sample that was collected within 6 months before initiating ibrutinib.
Disclosures: This study was supported in part by the Italian Ministry of Health “Progetto Ricerca Finalizzata” and others. The authors declared no conflicts of interest.
Source: Bomben R et al. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: A campus CLL study. Leukemia. 2023 (Feb 18). Doi: 10.1038/s41375-023-01845-9
Grade 3B FL prognostically similar to grade 3A FL but distinct from DLBCL
Key clinical point: Grade 3B follicular lymphoma (G3BFL) has similar survival outcomes to grade 3A FL (G3AFL) but a superior prognosis than diffuse large B-cell lymphoma (DLBCL) in immunotherapy-treated patients.
Major finding: At a median follow-up of 5 years, the G3BFL vs DLBCL group had a significantly longer progression-free survival (PFS; hazard ratio [HR] 1.73; P = .001) and overall survival (OS; HR 2.19; P ≤ .001), whereas PFS (HR 1.04; P = .81) and OS (HR 1.04; P = .84) were similar between the G3BFL and G3AFL groups.
Study details: This multicenter study analyzed the data of 157 patients with G3BFL, 302 patients with G3AFL, and 548 patients with DLBCL treated with rituximab/obinutuzumab, cyclophosphamide, doxorubicin, vincristine, and prednisolone-like chemotherapy with or without radiotherapy or bendamustine-rituximab.
Disclosures: The study did not receive any funding. Some authors reported ties with various organizations.
Source: Barraclough A et al. Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance. Haematologica. 2023 (Feb 23). Doi: 10.3324/haematol.2022.281375
Key clinical point: Grade 3B follicular lymphoma (G3BFL) has similar survival outcomes to grade 3A FL (G3AFL) but a superior prognosis than diffuse large B-cell lymphoma (DLBCL) in immunotherapy-treated patients.
Major finding: At a median follow-up of 5 years, the G3BFL vs DLBCL group had a significantly longer progression-free survival (PFS; hazard ratio [HR] 1.73; P = .001) and overall survival (OS; HR 2.19; P ≤ .001), whereas PFS (HR 1.04; P = .81) and OS (HR 1.04; P = .84) were similar between the G3BFL and G3AFL groups.
Study details: This multicenter study analyzed the data of 157 patients with G3BFL, 302 patients with G3AFL, and 548 patients with DLBCL treated with rituximab/obinutuzumab, cyclophosphamide, doxorubicin, vincristine, and prednisolone-like chemotherapy with or without radiotherapy or bendamustine-rituximab.
Disclosures: The study did not receive any funding. Some authors reported ties with various organizations.
Source: Barraclough A et al. Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance. Haematologica. 2023 (Feb 23). Doi: 10.3324/haematol.2022.281375
Key clinical point: Grade 3B follicular lymphoma (G3BFL) has similar survival outcomes to grade 3A FL (G3AFL) but a superior prognosis than diffuse large B-cell lymphoma (DLBCL) in immunotherapy-treated patients.
Major finding: At a median follow-up of 5 years, the G3BFL vs DLBCL group had a significantly longer progression-free survival (PFS; hazard ratio [HR] 1.73; P = .001) and overall survival (OS; HR 2.19; P ≤ .001), whereas PFS (HR 1.04; P = .81) and OS (HR 1.04; P = .84) were similar between the G3BFL and G3AFL groups.
Study details: This multicenter study analyzed the data of 157 patients with G3BFL, 302 patients with G3AFL, and 548 patients with DLBCL treated with rituximab/obinutuzumab, cyclophosphamide, doxorubicin, vincristine, and prednisolone-like chemotherapy with or without radiotherapy or bendamustine-rituximab.
Disclosures: The study did not receive any funding. Some authors reported ties with various organizations.
Source: Barraclough A et al. Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance. Haematologica. 2023 (Feb 23). Doi: 10.3324/haematol.2022.281375
No benefit of adding ibrutinib to chemoimmunotherapy in relapsed/refractory mature B-cell non-Hodgkin lymphoma
Key clinical point: Addition of ibrutinib to rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) provided no survival benefit in children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL).
Major finding: Patients receiving ibrutinib plus RICE/RVICI vs RICE/RVICI alone had similar median event-free survival (6.1 vs 7.0 months; hazard ratio [HR] 0.9; P = .387) and median overall survival (14.1 vs 11.1 months; HR 0.9; P = .789). All patients experienced grade ≥3 treatment-emergent adverse events.
Study details: Findings represent the final results of SPARKLE trial Part 2 that included 51 patients aged 1-30 years with relapsed or refractory mature B-NHL who were randomly assigned to receive ibrutinib plus RICE/RVICI (n = 35) or RICE/RVICI alone (n = 16).
Disclosures: This study was funded by Janssen Research and Development. Some authors reported ties with various organizations, including Janssen. Six authors declared being employees of Janssen or holding stocks in Johnson & Johnson.
Source: Burke GAA et al. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023;7(4):602-610 (Feb 20). Doi: 10.1182/bloodadvances.2022008802
Key clinical point: Addition of ibrutinib to rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) provided no survival benefit in children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL).
Major finding: Patients receiving ibrutinib plus RICE/RVICI vs RICE/RVICI alone had similar median event-free survival (6.1 vs 7.0 months; hazard ratio [HR] 0.9; P = .387) and median overall survival (14.1 vs 11.1 months; HR 0.9; P = .789). All patients experienced grade ≥3 treatment-emergent adverse events.
Study details: Findings represent the final results of SPARKLE trial Part 2 that included 51 patients aged 1-30 years with relapsed or refractory mature B-NHL who were randomly assigned to receive ibrutinib plus RICE/RVICI (n = 35) or RICE/RVICI alone (n = 16).
Disclosures: This study was funded by Janssen Research and Development. Some authors reported ties with various organizations, including Janssen. Six authors declared being employees of Janssen or holding stocks in Johnson & Johnson.
Source: Burke GAA et al. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023;7(4):602-610 (Feb 20). Doi: 10.1182/bloodadvances.2022008802
Key clinical point: Addition of ibrutinib to rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) provided no survival benefit in children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL).
Major finding: Patients receiving ibrutinib plus RICE/RVICI vs RICE/RVICI alone had similar median event-free survival (6.1 vs 7.0 months; hazard ratio [HR] 0.9; P = .387) and median overall survival (14.1 vs 11.1 months; HR 0.9; P = .789). All patients experienced grade ≥3 treatment-emergent adverse events.
Study details: Findings represent the final results of SPARKLE trial Part 2 that included 51 patients aged 1-30 years with relapsed or refractory mature B-NHL who were randomly assigned to receive ibrutinib plus RICE/RVICI (n = 35) or RICE/RVICI alone (n = 16).
Disclosures: This study was funded by Janssen Research and Development. Some authors reported ties with various organizations, including Janssen. Six authors declared being employees of Janssen or holding stocks in Johnson & Johnson.
Source: Burke GAA et al. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023;7(4):602-610 (Feb 20). Doi: 10.1182/bloodadvances.2022008802
Zanubrutinib elicits favorable long-term responses in relapsed or refractory CLL or SLL
Key clinical point: Long-term zanubrutinib monotherapy continued to yield high response and survival rates in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without compromising safety.
Major finding: At a median follow-up of 34 months, the overall response rate was 87.9% (95% CI 79.4%-93.8%). The median progression-free survival (PFS) or overall survival (OS) was not reached; the estimated PFS event-free and OS rates at 30 months were 75.7% (95% CI 65.2%-83.4%) and 88.6% (95% CI 79.8%-93.7%), respectively. No new safety signals were identified.
Study details: This long-term follow-up analysis of a phase 2 study included 91 patients with CLL/SLL who relapsed after or were refractory to ≥1 prior line of therapy and received 160 mg oral zanubrutinib twice daily.
Disclosures: The phase 2 study was sponsored by BeiGene (Beijing) Co., Ltd., China, and BeiGene USA, Inc., USA. Some authors declared being employees of and holding stocks in BeiGene.
Source: Xu W et al. Zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Final results and correlative analysis of lymphocytosis. Leuk Lymphoma. 2023;1-5 (Feb 17). Doi: 10.1080/10428194.2022.2164692
Key clinical point: Long-term zanubrutinib monotherapy continued to yield high response and survival rates in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without compromising safety.
Major finding: At a median follow-up of 34 months, the overall response rate was 87.9% (95% CI 79.4%-93.8%). The median progression-free survival (PFS) or overall survival (OS) was not reached; the estimated PFS event-free and OS rates at 30 months were 75.7% (95% CI 65.2%-83.4%) and 88.6% (95% CI 79.8%-93.7%), respectively. No new safety signals were identified.
Study details: This long-term follow-up analysis of a phase 2 study included 91 patients with CLL/SLL who relapsed after or were refractory to ≥1 prior line of therapy and received 160 mg oral zanubrutinib twice daily.
Disclosures: The phase 2 study was sponsored by BeiGene (Beijing) Co., Ltd., China, and BeiGene USA, Inc., USA. Some authors declared being employees of and holding stocks in BeiGene.
Source: Xu W et al. Zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Final results and correlative analysis of lymphocytosis. Leuk Lymphoma. 2023;1-5 (Feb 17). Doi: 10.1080/10428194.2022.2164692
Key clinical point: Long-term zanubrutinib monotherapy continued to yield high response and survival rates in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without compromising safety.
Major finding: At a median follow-up of 34 months, the overall response rate was 87.9% (95% CI 79.4%-93.8%). The median progression-free survival (PFS) or overall survival (OS) was not reached; the estimated PFS event-free and OS rates at 30 months were 75.7% (95% CI 65.2%-83.4%) and 88.6% (95% CI 79.8%-93.7%), respectively. No new safety signals were identified.
Study details: This long-term follow-up analysis of a phase 2 study included 91 patients with CLL/SLL who relapsed after or were refractory to ≥1 prior line of therapy and received 160 mg oral zanubrutinib twice daily.
Disclosures: The phase 2 study was sponsored by BeiGene (Beijing) Co., Ltd., China, and BeiGene USA, Inc., USA. Some authors declared being employees of and holding stocks in BeiGene.
Source: Xu W et al. Zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Final results and correlative analysis of lymphocytosis. Leuk Lymphoma. 2023;1-5 (Feb 17). Doi: 10.1080/10428194.2022.2164692
Chronic lymphocytic leukemia: A risk factor for poor outcomes in patients hospitalized with immune thrombocytopenia
Key clinical point: Patients hospitalized with immune thrombocytopenia (ITP) and concomitant chronic lymphocytic leukemia (CLL) have a greater risk for death, require more blood products, and have poorer hospitalization outcomes compared with those with ITP without CLL.
Major finding: The risks for all-cause mortality (adjusted odds ratio [aOR] 1.28), gastrointestinal bleeding (aOR 1.19), packed red blood cell transfusion (aOR 1.79), splenectomy (aOR 1.30), and platelet transfusion (aOR, 1.49) were higher in patients with ITP and CLL vs those with ITP without CLL (all P < .01).
Study details: The data come from a retrospective study including patients hospitalized for ITP who did (n = 15,672) and did not (n = 646,499) have concurrent CLL.
Disclosures: This study did not report the source of funding. Some authors declared receiving research grants or consulting fees from various sources.
Source: Ammad Ud Din M et al. Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: An analysis of the National Inpatient Sample Database. Ann Hematol. 2023;102(4):889-895 (Feb 13). Doi: 10.1007/s00277-023-05133-5
Key clinical point: Patients hospitalized with immune thrombocytopenia (ITP) and concomitant chronic lymphocytic leukemia (CLL) have a greater risk for death, require more blood products, and have poorer hospitalization outcomes compared with those with ITP without CLL.
Major finding: The risks for all-cause mortality (adjusted odds ratio [aOR] 1.28), gastrointestinal bleeding (aOR 1.19), packed red blood cell transfusion (aOR 1.79), splenectomy (aOR 1.30), and platelet transfusion (aOR, 1.49) were higher in patients with ITP and CLL vs those with ITP without CLL (all P < .01).
Study details: The data come from a retrospective study including patients hospitalized for ITP who did (n = 15,672) and did not (n = 646,499) have concurrent CLL.
Disclosures: This study did not report the source of funding. Some authors declared receiving research grants or consulting fees from various sources.
Source: Ammad Ud Din M et al. Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: An analysis of the National Inpatient Sample Database. Ann Hematol. 2023;102(4):889-895 (Feb 13). Doi: 10.1007/s00277-023-05133-5
Key clinical point: Patients hospitalized with immune thrombocytopenia (ITP) and concomitant chronic lymphocytic leukemia (CLL) have a greater risk for death, require more blood products, and have poorer hospitalization outcomes compared with those with ITP without CLL.
Major finding: The risks for all-cause mortality (adjusted odds ratio [aOR] 1.28), gastrointestinal bleeding (aOR 1.19), packed red blood cell transfusion (aOR 1.79), splenectomy (aOR 1.30), and platelet transfusion (aOR, 1.49) were higher in patients with ITP and CLL vs those with ITP without CLL (all P < .01).
Study details: The data come from a retrospective study including patients hospitalized for ITP who did (n = 15,672) and did not (n = 646,499) have concurrent CLL.
Disclosures: This study did not report the source of funding. Some authors declared receiving research grants or consulting fees from various sources.
Source: Ammad Ud Din M et al. Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: An analysis of the National Inpatient Sample Database. Ann Hematol. 2023;102(4):889-895 (Feb 13). Doi: 10.1007/s00277-023-05133-5
Long-term benefits of axicabtagene ciloleucel in refractory large B-cell lymphoma
Key clinical point: Axicabtagene ciloleucel (axi-cel) led to a durable response and long-term survival in patients with refractory large B-cell lymphoma (LBCL), with no new safety signals.
Major finding: At a median follow-up of 63.1 months from infusion, the objective and complete response rates were 83% (95% CI 74%-90%) and 58% (95% CI 48%-68%), respectively. The median overall survival (OS) was 25.8 (95% CI 12.8-not estimable) months, and the 5-year OS rate was 42.6% (95% CI 32.8%-51.9%). No new treatment-related adverse events were observed.
Study details: This 5-year follow-up analysis of the ZUMA-1 study phase 2 included 101 adult patients with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) who received lymphodepleting chemotherapy followed by axi-cel infusion.
Disclosures: This study was funded by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite. Seven authors declared being former or current employees of or holding stocks or having other ownership interests in Kite.
Source: Neelapu SS et al. 5-Year follow-up supports curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1). Blood. 2023 (Feb 23). Doi: 10.1182/blood.2022018893
Key clinical point: Axicabtagene ciloleucel (axi-cel) led to a durable response and long-term survival in patients with refractory large B-cell lymphoma (LBCL), with no new safety signals.
Major finding: At a median follow-up of 63.1 months from infusion, the objective and complete response rates were 83% (95% CI 74%-90%) and 58% (95% CI 48%-68%), respectively. The median overall survival (OS) was 25.8 (95% CI 12.8-not estimable) months, and the 5-year OS rate was 42.6% (95% CI 32.8%-51.9%). No new treatment-related adverse events were observed.
Study details: This 5-year follow-up analysis of the ZUMA-1 study phase 2 included 101 adult patients with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) who received lymphodepleting chemotherapy followed by axi-cel infusion.
Disclosures: This study was funded by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite. Seven authors declared being former or current employees of or holding stocks or having other ownership interests in Kite.
Source: Neelapu SS et al. 5-Year follow-up supports curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1). Blood. 2023 (Feb 23). Doi: 10.1182/blood.2022018893
Key clinical point: Axicabtagene ciloleucel (axi-cel) led to a durable response and long-term survival in patients with refractory large B-cell lymphoma (LBCL), with no new safety signals.
Major finding: At a median follow-up of 63.1 months from infusion, the objective and complete response rates were 83% (95% CI 74%-90%) and 58% (95% CI 48%-68%), respectively. The median overall survival (OS) was 25.8 (95% CI 12.8-not estimable) months, and the 5-year OS rate was 42.6% (95% CI 32.8%-51.9%). No new treatment-related adverse events were observed.
Study details: This 5-year follow-up analysis of the ZUMA-1 study phase 2 included 101 adult patients with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) who received lymphodepleting chemotherapy followed by axi-cel infusion.
Disclosures: This study was funded by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite. Seven authors declared being former or current employees of or holding stocks or having other ownership interests in Kite.
Source: Neelapu SS et al. 5-Year follow-up supports curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1). Blood. 2023 (Feb 23). Doi: 10.1182/blood.2022018893
Venetoclax may bridge to immunotherapy in relapsed/refractory mantle cell lymphoma
Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).
Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.
Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.
Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.
Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916
Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).
Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.
Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.
Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.
Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916
Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).
Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.
Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.
Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.
Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916