B-Cell Lymphoma ICYMI

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) led to acceptable survival outcomes in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), particularly in those achieving a partial or complete response to chemotherapy before allo-HSCT.

Major finding: At a median follow-up of 38.3 months, the estimated 5-year overall survival and event-free survival rates were 38.4% (95% CI 24.7%-51.8%) and 30.6% (95% CI 18.8%-43.3%), respectively, with patients who achieved a partial or complete response before allo-HSCT having overall survival and event-free survival rates of 54.1% (95% CI 34.2%-70.3%) and 46.4% (95% CI 28.1%-62.9%), respectively.

Study details: This retrospective study included 52 adult patients with relapsed or refractory DLBCL who either had an active disease status or achieved a partial or complete response before transplantation and underwent allo-HSCT.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Min GJ et al. The salvage role of allogeneic hematopoietic stem-cell transplantation in relapsed/refractory diffuse large B cell lymphoma. Sci Rep. 2023;13:17496 (Oct 15). doi: 10.1038/s41598-023-44241-0

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) led to acceptable survival outcomes in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), particularly in those achieving a partial or complete response to chemotherapy before allo-HSCT.

Major finding: At a median follow-up of 38.3 months, the estimated 5-year overall survival and event-free survival rates were 38.4% (95% CI 24.7%-51.8%) and 30.6% (95% CI 18.8%-43.3%), respectively, with patients who achieved a partial or complete response before allo-HSCT having overall survival and event-free survival rates of 54.1% (95% CI 34.2%-70.3%) and 46.4% (95% CI 28.1%-62.9%), respectively.

Study details: This retrospective study included 52 adult patients with relapsed or refractory DLBCL who either had an active disease status or achieved a partial or complete response before transplantation and underwent allo-HSCT.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Min GJ et al. The salvage role of allogeneic hematopoietic stem-cell transplantation in relapsed/refractory diffuse large B cell lymphoma. Sci Rep. 2023;13:17496 (Oct 15). doi: 10.1038/s41598-023-44241-0

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) led to acceptable survival outcomes in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), particularly in those achieving a partial or complete response to chemotherapy before allo-HSCT.

Major finding: At a median follow-up of 38.3 months, the estimated 5-year overall survival and event-free survival rates were 38.4% (95% CI 24.7%-51.8%) and 30.6% (95% CI 18.8%-43.3%), respectively, with patients who achieved a partial or complete response before allo-HSCT having overall survival and event-free survival rates of 54.1% (95% CI 34.2%-70.3%) and 46.4% (95% CI 28.1%-62.9%), respectively.

Study details: This retrospective study included 52 adult patients with relapsed or refractory DLBCL who either had an active disease status or achieved a partial or complete response before transplantation and underwent allo-HSCT.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Min GJ et al. The salvage role of allogeneic hematopoietic stem-cell transplantation in relapsed/refractory diffuse large B cell lymphoma. Sci Rep. 2023;13:17496 (Oct 15). doi: 10.1038/s41598-023-44241-0

Key clinical point: Fixed-duration ibrutinib-venetoclax vs chlorambucil-obinutuzumab continues to extend progression-free survival and leads to overall survival advantage at a 4-year follow-up in patients with previously untreated chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 46 months, the ibrutinib-venetoclax vs chlorambucil-obinutuzumab group continued to show better progression-free survival (hazard ratio [HR] 0.214; P < .0001) while also demonstrating overall survival benefit (HR 0.487; P  =  .021). One treatment-related death was reported in each group.

Study details: Findings are from a 4-year follow-up of the phase 3 GLOW trial including 211 patients with previously untreated CLL who were randomly assigned to receive ibrutinib-venetoclax or chlorambucil-obinutuzumab.

Disclosures: This study was funded by Janssen Research & Development and Pharmacyclics. Several authors declared serving on the boards of directors or advisory committees of or receiving consultancy fees, research funding, or honoraria from various sources, including Janssen. Nine authors declared being employees or equity holders of Janssen.

Source: Niemann CU et al. Fixed-duration ibrutinib–venetoclax versus chlorambucil–obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-Year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 (Nov 6). doi: 10.1016/S1470-2045(23)00452-7

Key clinical point: Fixed-duration ibrutinib-venetoclax vs chlorambucil-obinutuzumab continues to extend progression-free survival and leads to overall survival advantage at a 4-year follow-up in patients with previously untreated chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 46 months, the ibrutinib-venetoclax vs chlorambucil-obinutuzumab group continued to show better progression-free survival (hazard ratio [HR] 0.214; P < .0001) while also demonstrating overall survival benefit (HR 0.487; P  =  .021). One treatment-related death was reported in each group.

Study details: Findings are from a 4-year follow-up of the phase 3 GLOW trial including 211 patients with previously untreated CLL who were randomly assigned to receive ibrutinib-venetoclax or chlorambucil-obinutuzumab.

Disclosures: This study was funded by Janssen Research & Development and Pharmacyclics. Several authors declared serving on the boards of directors or advisory committees of or receiving consultancy fees, research funding, or honoraria from various sources, including Janssen. Nine authors declared being employees or equity holders of Janssen.

Source: Niemann CU et al. Fixed-duration ibrutinib–venetoclax versus chlorambucil–obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-Year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 (Nov 6). doi: 10.1016/S1470-2045(23)00452-7

Key clinical point: Fixed-duration ibrutinib-venetoclax vs chlorambucil-obinutuzumab continues to extend progression-free survival and leads to overall survival advantage at a 4-year follow-up in patients with previously untreated chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 46 months, the ibrutinib-venetoclax vs chlorambucil-obinutuzumab group continued to show better progression-free survival (hazard ratio [HR] 0.214; P < .0001) while also demonstrating overall survival benefit (HR 0.487; P  =  .021). One treatment-related death was reported in each group.

Study details: Findings are from a 4-year follow-up of the phase 3 GLOW trial including 211 patients with previously untreated CLL who were randomly assigned to receive ibrutinib-venetoclax or chlorambucil-obinutuzumab.

Disclosures: This study was funded by Janssen Research & Development and Pharmacyclics. Several authors declared serving on the boards of directors or advisory committees of or receiving consultancy fees, research funding, or honoraria from various sources, including Janssen. Nine authors declared being employees or equity holders of Janssen.

Source: Niemann CU et al. Fixed-duration ibrutinib–venetoclax versus chlorambucil–obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-Year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 (Nov 6). doi: 10.1016/S1470-2045(23)00452-7

Key clinical point: Brexucabtagene autoleucel (brexu-cel) provides survival benefit over non-chimeric antigen receptor (CAR) T-cell standard of care (SOC) in patients with relapsed or refractory mantle cell lymphoma (MCL) treated with covalent Bruton tyrosine kinase inhibitors (BTKi).

Major finding: Inverse probability weighting showed that brexu-cel vs SOC led to a significantly reduced risk for death (adjusted hazard ratio 0.38; P < .001), with the findings being similar for other adjusted comparisons.

Study details: This indirect comparison study analyzed the individual patient data of BTKi-treated patients with relapsed or refractory MCL who received brexu-cel in ZUMA-2 (n = 68) and non-CAR T-cell SOC in SCHOLAR-2 (n = 149).

Disclosures: This study was sponsored by Kite, a Gilead Company. Some authors declared participating in the data safety monitoring or advisory boards of or receiving grants, consulting fees, travel support, or honoraria for lectures, etc., from Kite, Gilead, and others. Five authors declared being employees or stockowners of Kite, Gilead, or PRECISIONheor.

Source: Hess G et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leuk Lymphoma. 2023 (Oct 16). doi: 10.1080/10428194.2023.2268228

Key clinical point: Brexucabtagene autoleucel (brexu-cel) provides survival benefit over non-chimeric antigen receptor (CAR) T-cell standard of care (SOC) in patients with relapsed or refractory mantle cell lymphoma (MCL) treated with covalent Bruton tyrosine kinase inhibitors (BTKi).

Major finding: Inverse probability weighting showed that brexu-cel vs SOC led to a significantly reduced risk for death (adjusted hazard ratio 0.38; P < .001), with the findings being similar for other adjusted comparisons.

Study details: This indirect comparison study analyzed the individual patient data of BTKi-treated patients with relapsed or refractory MCL who received brexu-cel in ZUMA-2 (n = 68) and non-CAR T-cell SOC in SCHOLAR-2 (n = 149).

Disclosures: This study was sponsored by Kite, a Gilead Company. Some authors declared participating in the data safety monitoring or advisory boards of or receiving grants, consulting fees, travel support, or honoraria for lectures, etc., from Kite, Gilead, and others. Five authors declared being employees or stockowners of Kite, Gilead, or PRECISIONheor.

Source: Hess G et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leuk Lymphoma. 2023 (Oct 16). doi: 10.1080/10428194.2023.2268228

Key clinical point: Brexucabtagene autoleucel (brexu-cel) provides survival benefit over non-chimeric antigen receptor (CAR) T-cell standard of care (SOC) in patients with relapsed or refractory mantle cell lymphoma (MCL) treated with covalent Bruton tyrosine kinase inhibitors (BTKi).

Major finding: Inverse probability weighting showed that brexu-cel vs SOC led to a significantly reduced risk for death (adjusted hazard ratio 0.38; P < .001), with the findings being similar for other adjusted comparisons.

Study details: This indirect comparison study analyzed the individual patient data of BTKi-treated patients with relapsed or refractory MCL who received brexu-cel in ZUMA-2 (n = 68) and non-CAR T-cell SOC in SCHOLAR-2 (n = 149).

Disclosures: This study was sponsored by Kite, a Gilead Company. Some authors declared participating in the data safety monitoring or advisory boards of or receiving grants, consulting fees, travel support, or honoraria for lectures, etc., from Kite, Gilead, and others. Five authors declared being employees or stockowners of Kite, Gilead, or PRECISIONheor.

Source: Hess G et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leuk Lymphoma. 2023 (Oct 16). doi: 10.1080/10428194.2023.2268228

Key clinical point: Patients with relapsed or refractory large B-cell lymphoma (LBCL) who were recently exposed to preapheresis bendamustine showed negative treatment outcomes, hematologic toxicity, and severe infections after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.

Major finding: Patients recently exposed to bendamustine (<9 months) vs those naive to it before apheresis had a significantly lower overall response rate (40% vs 66%; P  =  .01) and shorter overall survival (adjusted hazard ratio [aHR] 2.11; P < .01) and progression-free survival (aHR 1.82; P < .01) after CAR T-cell infusion.

Study details: This retrospective multicenter study included 439 patients with relapsed or refractory LBCL who received CD19-targeted commercial CAR T-cell therapy after ≥2 prior treatment lines, of whom 80 patients had received bendamustine before apheresis.

Disclosures: This study was supported by the Carlos III Health Institute, Spain, and others. Some authors declared serving in consulting or advisory roles for or as members of speakers’ bureaus of or receiving honoraria, research funding, or travel or accommodation expenses from various sources.

Source: Iacoboni G et al. Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy. J Clin Oncol. 2023 (Oct 24). doi: 10.1200/JCO.23.01097

Key clinical point: Patients with relapsed or refractory large B-cell lymphoma (LBCL) who were recently exposed to preapheresis bendamustine showed negative treatment outcomes, hematologic toxicity, and severe infections after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.

Major finding: Patients recently exposed to bendamustine (<9 months) vs those naive to it before apheresis had a significantly lower overall response rate (40% vs 66%; P  =  .01) and shorter overall survival (adjusted hazard ratio [aHR] 2.11; P < .01) and progression-free survival (aHR 1.82; P < .01) after CAR T-cell infusion.

Study details: This retrospective multicenter study included 439 patients with relapsed or refractory LBCL who received CD19-targeted commercial CAR T-cell therapy after ≥2 prior treatment lines, of whom 80 patients had received bendamustine before apheresis.

Disclosures: This study was supported by the Carlos III Health Institute, Spain, and others. Some authors declared serving in consulting or advisory roles for or as members of speakers’ bureaus of or receiving honoraria, research funding, or travel or accommodation expenses from various sources.

Source: Iacoboni G et al. Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy. J Clin Oncol. 2023 (Oct 24). doi: 10.1200/JCO.23.01097

Key clinical point: Patients with relapsed or refractory large B-cell lymphoma (LBCL) who were recently exposed to preapheresis bendamustine showed negative treatment outcomes, hematologic toxicity, and severe infections after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.

Major finding: Patients recently exposed to bendamustine (<9 months) vs those naive to it before apheresis had a significantly lower overall response rate (40% vs 66%; P  =  .01) and shorter overall survival (adjusted hazard ratio [aHR] 2.11; P < .01) and progression-free survival (aHR 1.82; P < .01) after CAR T-cell infusion.

Study details: This retrospective multicenter study included 439 patients with relapsed or refractory LBCL who received CD19-targeted commercial CAR T-cell therapy after ≥2 prior treatment lines, of whom 80 patients had received bendamustine before apheresis.

Disclosures: This study was supported by the Carlos III Health Institute, Spain, and others. Some authors declared serving in consulting or advisory roles for or as members of speakers’ bureaus of or receiving honoraria, research funding, or travel or accommodation expenses from various sources.

Source: Iacoboni G et al. Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy. J Clin Oncol. 2023 (Oct 24). doi: 10.1200/JCO.23.01097

The ZUMA-7 and TRANSFORM studies have been practice-changing for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). These studies demonstrated an improvement in outcomes with axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), respectively, as compared with standard-of-care treatment (chemotherapy and autologous stem cell transplantation).^1,2 Patients included in these studies were refractory to their initial therapy or experienced relapse within 12 months and were considered fit for autologous stem cell transplant. It has remained unclear, however, whether patients who are not transplant candidates may also derive benefit and tolerate treatment with chimeric antigen receptor (CAR) T-cell therapy. The PILOT study was a single-arm phase 2 study that demonstrated favorable outcomes with liso-cel in this patient population, thus resulting in the approval of liso-cel by the US Food and Drug Administration for this population.³ Recently, the ALYCATE study similarly examined outcomes in transplant-ineligible patients treated with axi-cel (Houot et al). This phase 2 study included 62 patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel. The complete metabolic response rate 3 months after axi-cel infusion was 71.0% (95% CI 58.1%-81.8%). At a median 12-month follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥ 3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 8.1% and 14.5% of patients, respectively. Also of note, patients age ≥ 70 years did not show increased toxicity compared with those age < 70 years, with similar rates of CRS, ICANS, and intensive care unit transfer. This study supports the role of axi-cel in the second-line setting, regardless of transplant eligibility.

Another important study recently published for patients with LBCL examined the role of central nervous system (CNS) prophylaxis (Lewis et al). We know that certain patients with LBCL, including those with a high CNS international prognostic index (IPI) score, double-hit lymphoma, or disease involvement of multiple or certain extranodal sites (ie, breast, testes, adrenals, kidney) can be at increased risk for lymphoma spread to the CNS.⁴ Strategies to reduce this risk have subsequently been developed for these high-risk patients, though consensus regarding who should be treated and how best to treat patients has been consistent. Recently, retrospective data have also called into question whether our current approaches meaningfully reduce this risk. One such study was a multicenter, international, retrospective observational study that included 2418 adults with aggressive LBCL and a high risk for CNS progression who were treated with curative-intent anti-CD20–based chemoimmunotherapy and who did or did not receive high-dose methotrexate (HD-MTX). Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those patients who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30). The study was not sufficiently powered to make definitive conclusions for individual risk groups, though there was no obvious reduction in CNS involvement risk in any high-risk subgroup. With an absolute risk reduction of 1.6% with the use of HD-MTX, 63 patients would require treatment to prevent one CNS progression event over 5 years (Lewis et al). Given the absence of prospective, randomized data, these results, though retrospective in nature, call into question the benefit of CNS prophylaxis. The authors suggest that studies evaluating alternative strategies for prophylaxis and tools for early detection of relapse, such as circulating tumor DNA, may be helpful.

Another study worth noting was one exploring Bruton tyrosine kinase (BTK) inhibition in mantle cell lymphoma (MCL). BTK inhibitors, including zanubrutinib, have emerged as effective therapies for patients with R/R disease. A recent pooled analysis included 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had R/R MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib (Song et al). At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (aHR 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib. These findings were in line with a prior similar pooled study that demonstrated improved outcomes with second-line ibrutinib for patients with MCL as compared with later-line ibrutinib therapy.⁵ This study, however, did not evaluate the impact on CAR T–cell therapy in MCL, which is also an effective treatment option for patients with R/R disease, and how best to sequence with BTK inhibitors.

Additional References

1.       Locke FL, Miklos DB, Jacobson CA, et al, for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

2.       Kamdar M, Solomon SR, Arnason J, et al, for theTRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6

3.       Gordon LI, Liu FF, Braverman J, et al. Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: Patient-reported outcomes from the PILOT study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283162

4.       Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016;34:3150-3156. doi: 10.1200/JCO.2015.65.6520

5.       Dreyling M, Goy A, Hess G, et al. Long-term outcomes with ibrutinib treatment for patients with relapsed/refractory mantle cell lymphoma: A pooled analysis of 3 clinical trials with nearly 10 years of follow-up. Hemasphere. 2022;6:e712. doi: 10.1097/HS9.0000000000000712

The ZUMA-7 and TRANSFORM studies have been practice-changing for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). These studies demonstrated an improvement in outcomes with axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), respectively, as compared with standard-of-care treatment (chemotherapy and autologous stem cell transplantation).^1,2 Patients included in these studies were refractory to their initial therapy or experienced relapse within 12 months and were considered fit for autologous stem cell transplant. It has remained unclear, however, whether patients who are not transplant candidates may also derive benefit and tolerate treatment with chimeric antigen receptor (CAR) T-cell therapy. The PILOT study was a single-arm phase 2 study that demonstrated favorable outcomes with liso-cel in this patient population, thus resulting in the approval of liso-cel by the US Food and Drug Administration for this population.³ Recently, the ALYCATE study similarly examined outcomes in transplant-ineligible patients treated with axi-cel (Houot et al). This phase 2 study included 62 patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel. The complete metabolic response rate 3 months after axi-cel infusion was 71.0% (95% CI 58.1%-81.8%). At a median 12-month follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥ 3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 8.1% and 14.5% of patients, respectively. Also of note, patients age ≥ 70 years did not show increased toxicity compared with those age < 70 years, with similar rates of CRS, ICANS, and intensive care unit transfer. This study supports the role of axi-cel in the second-line setting, regardless of transplant eligibility.

Another important study recently published for patients with LBCL examined the role of central nervous system (CNS) prophylaxis (Lewis et al). We know that certain patients with LBCL, including those with a high CNS international prognostic index (IPI) score, double-hit lymphoma, or disease involvement of multiple or certain extranodal sites (ie, breast, testes, adrenals, kidney) can be at increased risk for lymphoma spread to the CNS.⁴ Strategies to reduce this risk have subsequently been developed for these high-risk patients, though consensus regarding who should be treated and how best to treat patients has been consistent. Recently, retrospective data have also called into question whether our current approaches meaningfully reduce this risk. One such study was a multicenter, international, retrospective observational study that included 2418 adults with aggressive LBCL and a high risk for CNS progression who were treated with curative-intent anti-CD20–based chemoimmunotherapy and who did or did not receive high-dose methotrexate (HD-MTX). Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those patients who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30). The study was not sufficiently powered to make definitive conclusions for individual risk groups, though there was no obvious reduction in CNS involvement risk in any high-risk subgroup. With an absolute risk reduction of 1.6% with the use of HD-MTX, 63 patients would require treatment to prevent one CNS progression event over 5 years (Lewis et al). Given the absence of prospective, randomized data, these results, though retrospective in nature, call into question the benefit of CNS prophylaxis. The authors suggest that studies evaluating alternative strategies for prophylaxis and tools for early detection of relapse, such as circulating tumor DNA, may be helpful.

Another study worth noting was one exploring Bruton tyrosine kinase (BTK) inhibition in mantle cell lymphoma (MCL). BTK inhibitors, including zanubrutinib, have emerged as effective therapies for patients with R/R disease. A recent pooled analysis included 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had R/R MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib (Song et al). At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (aHR 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib. These findings were in line with a prior similar pooled study that demonstrated improved outcomes with second-line ibrutinib for patients with MCL as compared with later-line ibrutinib therapy.⁵ This study, however, did not evaluate the impact on CAR T–cell therapy in MCL, which is also an effective treatment option for patients with R/R disease, and how best to sequence with BTK inhibitors.

Additional References

1.       Locke FL, Miklos DB, Jacobson CA, et al, for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

2.       Kamdar M, Solomon SR, Arnason J, et al, for theTRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6

3.       Gordon LI, Liu FF, Braverman J, et al. Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: Patient-reported outcomes from the PILOT study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283162

4.       Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016;34:3150-3156. doi: 10.1200/JCO.2015.65.6520

5.       Dreyling M, Goy A, Hess G, et al. Long-term outcomes with ibrutinib treatment for patients with relapsed/refractory mantle cell lymphoma: A pooled analysis of 3 clinical trials with nearly 10 years of follow-up. Hemasphere. 2022;6:e712. doi: 10.1097/HS9.0000000000000712

The ZUMA-7 and TRANSFORM studies have been practice-changing for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). These studies demonstrated an improvement in outcomes with axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), respectively, as compared with standard-of-care treatment (chemotherapy and autologous stem cell transplantation).^1,2 Patients included in these studies were refractory to their initial therapy or experienced relapse within 12 months and were considered fit for autologous stem cell transplant. It has remained unclear, however, whether patients who are not transplant candidates may also derive benefit and tolerate treatment with chimeric antigen receptor (CAR) T-cell therapy. The PILOT study was a single-arm phase 2 study that demonstrated favorable outcomes with liso-cel in this patient population, thus resulting in the approval of liso-cel by the US Food and Drug Administration for this population.³ Recently, the ALYCATE study similarly examined outcomes in transplant-ineligible patients treated with axi-cel (Houot et al). This phase 2 study included 62 patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel. The complete metabolic response rate 3 months after axi-cel infusion was 71.0% (95% CI 58.1%-81.8%). At a median 12-month follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥ 3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 8.1% and 14.5% of patients, respectively. Also of note, patients age ≥ 70 years did not show increased toxicity compared with those age < 70 years, with similar rates of CRS, ICANS, and intensive care unit transfer. This study supports the role of axi-cel in the second-line setting, regardless of transplant eligibility.

Another important study recently published for patients with LBCL examined the role of central nervous system (CNS) prophylaxis (Lewis et al). We know that certain patients with LBCL, including those with a high CNS international prognostic index (IPI) score, double-hit lymphoma, or disease involvement of multiple or certain extranodal sites (ie, breast, testes, adrenals, kidney) can be at increased risk for lymphoma spread to the CNS.⁴ Strategies to reduce this risk have subsequently been developed for these high-risk patients, though consensus regarding who should be treated and how best to treat patients has been consistent. Recently, retrospective data have also called into question whether our current approaches meaningfully reduce this risk. One such study was a multicenter, international, retrospective observational study that included 2418 adults with aggressive LBCL and a high risk for CNS progression who were treated with curative-intent anti-CD20–based chemoimmunotherapy and who did or did not receive high-dose methotrexate (HD-MTX). Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those patients who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30). The study was not sufficiently powered to make definitive conclusions for individual risk groups, though there was no obvious reduction in CNS involvement risk in any high-risk subgroup. With an absolute risk reduction of 1.6% with the use of HD-MTX, 63 patients would require treatment to prevent one CNS progression event over 5 years (Lewis et al). Given the absence of prospective, randomized data, these results, though retrospective in nature, call into question the benefit of CNS prophylaxis. The authors suggest that studies evaluating alternative strategies for prophylaxis and tools for early detection of relapse, such as circulating tumor DNA, may be helpful.

Another study worth noting was one exploring Bruton tyrosine kinase (BTK) inhibition in mantle cell lymphoma (MCL). BTK inhibitors, including zanubrutinib, have emerged as effective therapies for patients with R/R disease. A recent pooled analysis included 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had R/R MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib (Song et al). At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (aHR 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib. These findings were in line with a prior similar pooled study that demonstrated improved outcomes with second-line ibrutinib for patients with MCL as compared with later-line ibrutinib therapy.⁵ This study, however, did not evaluate the impact on CAR T–cell therapy in MCL, which is also an effective treatment option for patients with R/R disease, and how best to sequence with BTK inhibitors.

Additional References

1.       Locke FL, Miklos DB, Jacobson CA, et al, for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

2.       Kamdar M, Solomon SR, Arnason J, et al, for theTRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6

3.       Gordon LI, Liu FF, Braverman J, et al. Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: Patient-reported outcomes from the PILOT study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283162

4.       Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016;34:3150-3156. doi: 10.1200/JCO.2015.65.6520

5.       Dreyling M, Goy A, Hess G, et al. Long-term outcomes with ibrutinib treatment for patients with relapsed/refractory mantle cell lymphoma: A pooled analysis of 3 clinical trials with nearly 10 years of follow-up. Hemasphere. 2022;6:e712. doi: 10.1097/HS9.0000000000000712

Key clinical point: Long-term exposure to brominated trihalomethanes (THM) in drinking water and swimming pool water is associated with increased odds of developing chronic lymphocytic leukemia (CLL).

Major finding: The odds of developing CLL increased by 22% for every 10 μg/L increase in the level of brominated THM in drinking water (adjusted odds ratio [aOR] 1.22; 95% CI 1.14-1.31). Swimming pool users vs non-users (swimming pool attendance ≥ 10 times vs < 10 times in life) had significantly increased odds of CLL (aOR 2.38; 95% CI 1.61-3.52).

Study details: This multicentric multicase-control study included 170 patients with CLL (age 20-85 years) and 1442 matched population-based control individuals without CLL.

Disclosures: This study was funded by European Commission grants and others. The authors declared no conflicts of interest.

Source: Donat-Vargas C et al. Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: A multicase-control study in Spain (MCC-Spain). J Expo Sci Environ Epidemiol. 2023 (Sep 19). doi: 10.1038/s41370-023-00600-7

Key clinical point: Long-term exposure to brominated trihalomethanes (THM) in drinking water and swimming pool water is associated with increased odds of developing chronic lymphocytic leukemia (CLL).

Major finding: The odds of developing CLL increased by 22% for every 10 μg/L increase in the level of brominated THM in drinking water (adjusted odds ratio [aOR] 1.22; 95% CI 1.14-1.31). Swimming pool users vs non-users (swimming pool attendance ≥ 10 times vs < 10 times in life) had significantly increased odds of CLL (aOR 2.38; 95% CI 1.61-3.52).

Study details: This multicentric multicase-control study included 170 patients with CLL (age 20-85 years) and 1442 matched population-based control individuals without CLL.

Disclosures: This study was funded by European Commission grants and others. The authors declared no conflicts of interest.

Source: Donat-Vargas C et al. Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: A multicase-control study in Spain (MCC-Spain). J Expo Sci Environ Epidemiol. 2023 (Sep 19). doi: 10.1038/s41370-023-00600-7

Key clinical point: Long-term exposure to brominated trihalomethanes (THM) in drinking water and swimming pool water is associated with increased odds of developing chronic lymphocytic leukemia (CLL).

Major finding: The odds of developing CLL increased by 22% for every 10 μg/L increase in the level of brominated THM in drinking water (adjusted odds ratio [aOR] 1.22; 95% CI 1.14-1.31). Swimming pool users vs non-users (swimming pool attendance ≥ 10 times vs < 10 times in life) had significantly increased odds of CLL (aOR 2.38; 95% CI 1.61-3.52).

Study details: This multicentric multicase-control study included 170 patients with CLL (age 20-85 years) and 1442 matched population-based control individuals without CLL.

Disclosures: This study was funded by European Commission grants and others. The authors declared no conflicts of interest.

Source: Donat-Vargas C et al. Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: A multicase-control study in Spain (MCC-Spain). J Expo Sci Environ Epidemiol. 2023 (Sep 19). doi: 10.1038/s41370-023-00600-7

Key clinical point: Chimeric antigen receptor (CAR) T-cell therapy is effective for and can be safely administered to older patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) despite an increased infection rate.

Major finding: At a median follow-up of 16.3 months, the objective response rate was 67%. Median progression-free and overall survival were 10.3 (95% CI 3.3-not reached) and 28.4 (95% CI 12.4-not reached) months, respectively. Patients age > 70 years and age ≤ 70 years had comparable progression-free (P = .6) and overall (P = .5) survival and comparable incidence rates of immune effector cell-associated neurotoxicity syndrome (P = .19); however, patients age > 70 years vs age ≤ 70 years had higher all-grade infection rates (79% vs 40%, respectively).

Study details: This single-center retrospective study included 66 patients with relapsed or refractory DLBCL who received either tisagenlecleucel or axicabtagene ciloleucel, of whom 21% were age > 70 years.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Trando A et al. Outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL): A single-institution experience. Cancers. 2023; 15(18):4671 (Sep 21). doi: 10.3390/cancers15184671

Key clinical point: Chimeric antigen receptor (CAR) T-cell therapy is effective for and can be safely administered to older patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) despite an increased infection rate.

Major finding: At a median follow-up of 16.3 months, the objective response rate was 67%. Median progression-free and overall survival were 10.3 (95% CI 3.3-not reached) and 28.4 (95% CI 12.4-not reached) months, respectively. Patients age > 70 years and age ≤ 70 years had comparable progression-free (P = .6) and overall (P = .5) survival and comparable incidence rates of immune effector cell-associated neurotoxicity syndrome (P = .19); however, patients age > 70 years vs age ≤ 70 years had higher all-grade infection rates (79% vs 40%, respectively).

Study details: This single-center retrospective study included 66 patients with relapsed or refractory DLBCL who received either tisagenlecleucel or axicabtagene ciloleucel, of whom 21% were age > 70 years.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Trando A et al. Outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL): A single-institution experience. Cancers. 2023; 15(18):4671 (Sep 21). doi: 10.3390/cancers15184671

Key clinical point: Chimeric antigen receptor (CAR) T-cell therapy is effective for and can be safely administered to older patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) despite an increased infection rate.

Major finding: At a median follow-up of 16.3 months, the objective response rate was 67%. Median progression-free and overall survival were 10.3 (95% CI 3.3-not reached) and 28.4 (95% CI 12.4-not reached) months, respectively. Patients age > 70 years and age ≤ 70 years had comparable progression-free (P = .6) and overall (P = .5) survival and comparable incidence rates of immune effector cell-associated neurotoxicity syndrome (P = .19); however, patients age > 70 years vs age ≤ 70 years had higher all-grade infection rates (79% vs 40%, respectively).

Study details: This single-center retrospective study included 66 patients with relapsed or refractory DLBCL who received either tisagenlecleucel or axicabtagene ciloleucel, of whom 21% were age > 70 years.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Trando A et al. Outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL): A single-institution experience. Cancers. 2023; 15(18):4671 (Sep 21). doi: 10.3390/cancers15184671

Key clinical point: Acalabrutinib and zanubrutinib showed similar efficacy and safety profiles in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) after matching observed patient variables that are prognostic or predictive at baseline.

Major finding: Acalabrutinib and zanubrutinib treatments resulted in comparable investigator-assessed progression-free survival outcomes (adjusted hazard ratio 0.90; 95% CI 0.60-1.36) and comparable risks for grade ≥3 adverse events (adjusted odds ratio 0.66; 95% CI 0.41-1.05).

Study details: This unanchored indirect comparison study included patients with relapsed or refractory CLL and matched the individual patient-level data of those who received acalabrutinib in the ASCEND trial (n = 149) with the aggregate data of those who received zanubrutinib in the ALPINE trial (n = 327).

Disclosures: This study was funded by AstraZeneca, USA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or consulting fees from various sources, including AstraZeneca. Six authors declared being employees of AstraZeneca, USA, or holding stocks in AstraZeneca.

Source: Kittai AS, Skarbnick A, et al. A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Am J Hematol. 2023 (Oct 9). doi: 10.1002/ajh.27110

Key clinical point: Acalabrutinib and zanubrutinib showed similar efficacy and safety profiles in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) after matching observed patient variables that are prognostic or predictive at baseline.

Major finding: Acalabrutinib and zanubrutinib treatments resulted in comparable investigator-assessed progression-free survival outcomes (adjusted hazard ratio 0.90; 95% CI 0.60-1.36) and comparable risks for grade ≥3 adverse events (adjusted odds ratio 0.66; 95% CI 0.41-1.05).

Study details: This unanchored indirect comparison study included patients with relapsed or refractory CLL and matched the individual patient-level data of those who received acalabrutinib in the ASCEND trial (n = 149) with the aggregate data of those who received zanubrutinib in the ALPINE trial (n = 327).

Disclosures: This study was funded by AstraZeneca, USA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or consulting fees from various sources, including AstraZeneca. Six authors declared being employees of AstraZeneca, USA, or holding stocks in AstraZeneca.

Source: Kittai AS, Skarbnick A, et al. A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Am J Hematol. 2023 (Oct 9). doi: 10.1002/ajh.27110

Key clinical point: Acalabrutinib and zanubrutinib showed similar efficacy and safety profiles in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) after matching observed patient variables that are prognostic or predictive at baseline.

Major finding: Acalabrutinib and zanubrutinib treatments resulted in comparable investigator-assessed progression-free survival outcomes (adjusted hazard ratio 0.90; 95% CI 0.60-1.36) and comparable risks for grade ≥3 adverse events (adjusted odds ratio 0.66; 95% CI 0.41-1.05).

Study details: This unanchored indirect comparison study included patients with relapsed or refractory CLL and matched the individual patient-level data of those who received acalabrutinib in the ASCEND trial (n = 149) with the aggregate data of those who received zanubrutinib in the ALPINE trial (n = 327).

Disclosures: This study was funded by AstraZeneca, USA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or consulting fees from various sources, including AstraZeneca. Six authors declared being employees of AstraZeneca, USA, or holding stocks in AstraZeneca.

Source: Kittai AS, Skarbnick A, et al. A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Am J Hematol. 2023 (Oct 9). doi: 10.1002/ajh.27110

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330