B Cell Lymphoma

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that is clinically heterogeneous, ranging from indolent to aggressive in nature. As with other subtypes of NHL, the treatment landscape is rapidly evolving.

Chemoimmunotherapy remains the standard first-line therapy for younger, fit patients. Although multiple induction regimens are used in this setting, it is typical to use a cytarabine-containing approach. Recently, the long-term analysis of the MCL Younger trial continued to demonstrate improved outcomes with this strategy.¹ This phase 3 study included 497 patients aged ≥ 18 to < 66 years with previously untreated MCL who were randomly assigned to R-CHOP (cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine; n = 249) or R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin; n = 248). After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer time to treatment failure (hazard ratio [HR] 0.59; P = .038) and overall survival (Mantle Cell Lymphoma International Prognostic Index + Ki-67–adjusted HR 0.60; P = .0066).

Following chemoimmunotherapy, treatment for this patient population typically consists of consolidation with autologous stem cell transplantation (ASCT) and maintenance rituximab.² Recently, the role of ASCT has been called into question.³ Preliminary data from the phase 3 TRIANGLE study demonstrated improvement in outcomes when the Bruton tyrosine kinase (BTK) inhibitor ibrutinib was added to chemoimmunotherapy, regardless of whether patients received ASCT.⁴ Additional studies evaluating the role of transplantation, particularly among patients who are minimal residual disease negative after chemoimmunotherapy, are ongoing (NCT03267433).

Options continue to expand in the relapsed/refractory setting. The chimeric antigen receptor (CAR) T-cell therapy, brexucabtagene autoleucel (brexu-cel), was approved by the US Food and Drug Administration for relapsed/refractory MCL on the basis of the results of the ZUMA-2 study.⁵ Recently, a multicenter, retrospective study demonstrated promising efficacy in the real world as well (Wang et al). This study was performed across 16 medical centers and included 189 patients with relapsed/refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion. Of all patients receiving leukapheresis, 149 (79%) would not have met the eligibility criteria for ZUMA-2. At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival (PFS) rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. This approach, however, was associated with significant toxicity, with a nonrelapse mortality rate of 9.1% at 1 year, primarily because of infections. The grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively. Despite risks, this study confirms the role of CAR T-cell therapy for patients with relapsed/refractory MCL.

Other options in the relapsed setting include BTK and anti-apoptotic protein B-cell lymphoma (BCL-2) inhibitors. Although venetoclax, a BCL-2 inhibitor, has demonstrated activity in MCL in early-phase clinical trials, the role of this drug in clinical practice remains unclear.^6,7 A recent multicenter, retrospective study evaluated the use of venetoclax in 81 adult patients with relapsed/refractory MCL, most of whom were heavily pretreated (median of three prior treatments) and had high-risk features, including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents (Sawalha et al). In this study, venetoclax resulted in a good overall response rate (ORR) but short PFS. At a median follow-up of 16.4 months, patients had a median PFS and overall survival of 3.7 months (95% CI 2.3-5.6) and 12.5 months (95% CI 6.2-28.2), respectively, and an ORR of 40%. Studies of venetoclax in earlier lines of therapy and in combination with other agents are ongoing. There may also be a role for this treatment as a bridge to more definitive therapies, including CAR T-cell therapy or allogeneic stem cell transplantation. Other studies that are evaluating the role of bispecific antibodies and antibody drug conjugates are also underway, suggesting the potential for additional options in this patient population.

Additional References

1.         Hermine O, Jiang L, Walewski J, et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023;41:479-484. doi: 10.1200/JCO.22.01780

2.         Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377:1250-1260. doi: 10.1056/NEJMoa1701769

3.         Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: Results from large real-world cohorts. J Clin Oncol. 2023;41:541-554. doi: 10.1200/JCO.21.02698

4.         Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: Results from the randomized Triangle Trial by the European MCL Network. Blood. 2022;140(Suppl 1):1-3. doi: 10.1182/blood-2022-163018

5.         Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331-1342. doi: 10.1056/NEJMoa1914347

6.         Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35:826-833. doi: 10.1200/JCO.2016.70.4320

7.         Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018;378:1211-1223. doi: 10.1056/NEJMoa1715519

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that is clinically heterogeneous, ranging from indolent to aggressive in nature. As with other subtypes of NHL, the treatment landscape is rapidly evolving.

Chemoimmunotherapy remains the standard first-line therapy for younger, fit patients. Although multiple induction regimens are used in this setting, it is typical to use a cytarabine-containing approach. Recently, the long-term analysis of the MCL Younger trial continued to demonstrate improved outcomes with this strategy.¹ This phase 3 study included 497 patients aged ≥ 18 to < 66 years with previously untreated MCL who were randomly assigned to R-CHOP (cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine; n = 249) or R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin; n = 248). After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer time to treatment failure (hazard ratio [HR] 0.59; P = .038) and overall survival (Mantle Cell Lymphoma International Prognostic Index + Ki-67–adjusted HR 0.60; P = .0066).

Following chemoimmunotherapy, treatment for this patient population typically consists of consolidation with autologous stem cell transplantation (ASCT) and maintenance rituximab.² Recently, the role of ASCT has been called into question.³ Preliminary data from the phase 3 TRIANGLE study demonstrated improvement in outcomes when the Bruton tyrosine kinase (BTK) inhibitor ibrutinib was added to chemoimmunotherapy, regardless of whether patients received ASCT.⁴ Additional studies evaluating the role of transplantation, particularly among patients who are minimal residual disease negative after chemoimmunotherapy, are ongoing (NCT03267433).

Options continue to expand in the relapsed/refractory setting. The chimeric antigen receptor (CAR) T-cell therapy, brexucabtagene autoleucel (brexu-cel), was approved by the US Food and Drug Administration for relapsed/refractory MCL on the basis of the results of the ZUMA-2 study.⁵ Recently, a multicenter, retrospective study demonstrated promising efficacy in the real world as well (Wang et al). This study was performed across 16 medical centers and included 189 patients with relapsed/refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion. Of all patients receiving leukapheresis, 149 (79%) would not have met the eligibility criteria for ZUMA-2. At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival (PFS) rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. This approach, however, was associated with significant toxicity, with a nonrelapse mortality rate of 9.1% at 1 year, primarily because of infections. The grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively. Despite risks, this study confirms the role of CAR T-cell therapy for patients with relapsed/refractory MCL.

Other options in the relapsed setting include BTK and anti-apoptotic protein B-cell lymphoma (BCL-2) inhibitors. Although venetoclax, a BCL-2 inhibitor, has demonstrated activity in MCL in early-phase clinical trials, the role of this drug in clinical practice remains unclear.^6,7 A recent multicenter, retrospective study evaluated the use of venetoclax in 81 adult patients with relapsed/refractory MCL, most of whom were heavily pretreated (median of three prior treatments) and had high-risk features, including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents (Sawalha et al). In this study, venetoclax resulted in a good overall response rate (ORR) but short PFS. At a median follow-up of 16.4 months, patients had a median PFS and overall survival of 3.7 months (95% CI 2.3-5.6) and 12.5 months (95% CI 6.2-28.2), respectively, and an ORR of 40%. Studies of venetoclax in earlier lines of therapy and in combination with other agents are ongoing. There may also be a role for this treatment as a bridge to more definitive therapies, including CAR T-cell therapy or allogeneic stem cell transplantation. Other studies that are evaluating the role of bispecific antibodies and antibody drug conjugates are also underway, suggesting the potential for additional options in this patient population.

Additional References

1.         Hermine O, Jiang L, Walewski J, et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023;41:479-484. doi: 10.1200/JCO.22.01780

2.         Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377:1250-1260. doi: 10.1056/NEJMoa1701769

3.         Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: Results from large real-world cohorts. J Clin Oncol. 2023;41:541-554. doi: 10.1200/JCO.21.02698

4.         Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: Results from the randomized Triangle Trial by the European MCL Network. Blood. 2022;140(Suppl 1):1-3. doi: 10.1182/blood-2022-163018

5.         Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331-1342. doi: 10.1056/NEJMoa1914347

6.         Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35:826-833. doi: 10.1200/JCO.2016.70.4320

7.         Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018;378:1211-1223. doi: 10.1056/NEJMoa1715519

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that is clinically heterogeneous, ranging from indolent to aggressive in nature. As with other subtypes of NHL, the treatment landscape is rapidly evolving.

Chemoimmunotherapy remains the standard first-line therapy for younger, fit patients. Although multiple induction regimens are used in this setting, it is typical to use a cytarabine-containing approach. Recently, the long-term analysis of the MCL Younger trial continued to demonstrate improved outcomes with this strategy.¹ This phase 3 study included 497 patients aged ≥ 18 to < 66 years with previously untreated MCL who were randomly assigned to R-CHOP (cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine; n = 249) or R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin; n = 248). After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer time to treatment failure (hazard ratio [HR] 0.59; P = .038) and overall survival (Mantle Cell Lymphoma International Prognostic Index + Ki-67–adjusted HR 0.60; P = .0066).

Following chemoimmunotherapy, treatment for this patient population typically consists of consolidation with autologous stem cell transplantation (ASCT) and maintenance rituximab.² Recently, the role of ASCT has been called into question.³ Preliminary data from the phase 3 TRIANGLE study demonstrated improvement in outcomes when the Bruton tyrosine kinase (BTK) inhibitor ibrutinib was added to chemoimmunotherapy, regardless of whether patients received ASCT.⁴ Additional studies evaluating the role of transplantation, particularly among patients who are minimal residual disease negative after chemoimmunotherapy, are ongoing (NCT03267433).

Options continue to expand in the relapsed/refractory setting. The chimeric antigen receptor (CAR) T-cell therapy, brexucabtagene autoleucel (brexu-cel), was approved by the US Food and Drug Administration for relapsed/refractory MCL on the basis of the results of the ZUMA-2 study.⁵ Recently, a multicenter, retrospective study demonstrated promising efficacy in the real world as well (Wang et al). This study was performed across 16 medical centers and included 189 patients with relapsed/refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion. Of all patients receiving leukapheresis, 149 (79%) would not have met the eligibility criteria for ZUMA-2. At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival (PFS) rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. This approach, however, was associated with significant toxicity, with a nonrelapse mortality rate of 9.1% at 1 year, primarily because of infections. The grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively. Despite risks, this study confirms the role of CAR T-cell therapy for patients with relapsed/refractory MCL.

Other options in the relapsed setting include BTK and anti-apoptotic protein B-cell lymphoma (BCL-2) inhibitors. Although venetoclax, a BCL-2 inhibitor, has demonstrated activity in MCL in early-phase clinical trials, the role of this drug in clinical practice remains unclear.^6,7 A recent multicenter, retrospective study evaluated the use of venetoclax in 81 adult patients with relapsed/refractory MCL, most of whom were heavily pretreated (median of three prior treatments) and had high-risk features, including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents (Sawalha et al). In this study, venetoclax resulted in a good overall response rate (ORR) but short PFS. At a median follow-up of 16.4 months, patients had a median PFS and overall survival of 3.7 months (95% CI 2.3-5.6) and 12.5 months (95% CI 6.2-28.2), respectively, and an ORR of 40%. Studies of venetoclax in earlier lines of therapy and in combination with other agents are ongoing. There may also be a role for this treatment as a bridge to more definitive therapies, including CAR T-cell therapy or allogeneic stem cell transplantation. Other studies that are evaluating the role of bispecific antibodies and antibody drug conjugates are also underway, suggesting the potential for additional options in this patient population.

Additional References

1.         Hermine O, Jiang L, Walewski J, et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023;41:479-484. doi: 10.1200/JCO.22.01780

2.         Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377:1250-1260. doi: 10.1056/NEJMoa1701769

3.         Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: Results from large real-world cohorts. J Clin Oncol. 2023;41:541-554. doi: 10.1200/JCO.21.02698

4.         Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: Results from the randomized Triangle Trial by the European MCL Network. Blood. 2022;140(Suppl 1):1-3. doi: 10.1182/blood-2022-163018

5.         Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331-1342. doi: 10.1056/NEJMoa1914347

6.         Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35:826-833. doi: 10.1200/JCO.2016.70.4320

7.         Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018;378:1211-1223. doi: 10.1056/NEJMoa1715519

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

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.

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

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.

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

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.

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.

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

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

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

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

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

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

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