Diffuse large B-cell lymphoma: No impact of lenalidomide after R-CHOP on unfavorable prognosis of low NK-cell counts

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Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

 

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

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Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

 

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

 

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

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Ibrutinib shows long-term benefits in chronic lymphocytic leukemia/small lymphocytic lymphoma in RESONATE-2

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Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

 

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

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Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

 

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

 

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

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Relapsed follicular lymphoma: Autologous stem cell transplantation shows long-term curative effects

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Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

 

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

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Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

 

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

 

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

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Second-line lisocabtagene maraleucel shows promise in large B-cell lymphoma

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Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

 

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×106 chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730

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Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

 

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×106 chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730

Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

 

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×106 chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730

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Mantle cell lymphoma: Real-world benefits of rituximab maintenance after first-line BR/R-CHOP

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Key clinical point: Rituximab maintenance (RM) therapy after first-line bendamustine-rituximab (BR) or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improved overall survival and disease control in older patients with mantle cell lymphoma (MCL).

 

Major finding: Patients who did vs did not receive RM therapy had a significantly longer overall survival (adjusted hazard ratio [aHR] 0.53; 95% CI 0.34-0.82) and approximated progression-free survival (survival or free of second-line therapy; aHR 0.51; 95% CI 0.36-0.72).

Study details: This real-world study included 131 propensity-score matched pairs of autologous stem cell transplant-ineligible patients aged ≥66 years with MCL who did and did not receive RM after first-line treatment with BR or R-CHOP.

Disclosures: This study did not receive any financial support. No information on conflicts of interest was reported.

Source: Di M et al. Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: A population-based analysis. Haematologica. 2023 (Jan 19). Doi: 10.3324/haematol.2022.282252

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Key clinical point: Rituximab maintenance (RM) therapy after first-line bendamustine-rituximab (BR) or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improved overall survival and disease control in older patients with mantle cell lymphoma (MCL).

 

Major finding: Patients who did vs did not receive RM therapy had a significantly longer overall survival (adjusted hazard ratio [aHR] 0.53; 95% CI 0.34-0.82) and approximated progression-free survival (survival or free of second-line therapy; aHR 0.51; 95% CI 0.36-0.72).

Study details: This real-world study included 131 propensity-score matched pairs of autologous stem cell transplant-ineligible patients aged ≥66 years with MCL who did and did not receive RM after first-line treatment with BR or R-CHOP.

Disclosures: This study did not receive any financial support. No information on conflicts of interest was reported.

Source: Di M et al. Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: A population-based analysis. Haematologica. 2023 (Jan 19). Doi: 10.3324/haematol.2022.282252

Key clinical point: Rituximab maintenance (RM) therapy after first-line bendamustine-rituximab (BR) or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improved overall survival and disease control in older patients with mantle cell lymphoma (MCL).

 

Major finding: Patients who did vs did not receive RM therapy had a significantly longer overall survival (adjusted hazard ratio [aHR] 0.53; 95% CI 0.34-0.82) and approximated progression-free survival (survival or free of second-line therapy; aHR 0.51; 95% CI 0.36-0.72).

Study details: This real-world study included 131 propensity-score matched pairs of autologous stem cell transplant-ineligible patients aged ≥66 years with MCL who did and did not receive RM after first-line treatment with BR or R-CHOP.

Disclosures: This study did not receive any financial support. No information on conflicts of interest was reported.

Source: Di M et al. Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: A population-based analysis. Haematologica. 2023 (Jan 19). Doi: 10.3324/haematol.2022.282252

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Bendamustine-rituximab effective in elderly with indolent non-Hodgkin's or mantle cell lymphoma

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Key clinical point: In the real-world setting, dose reductions and therapy delays are more common among elderly vs younger patients receiving first-line bendamustine-rituximab (BR) for indolent non-Hodgkin's lymphoma (iNHL) or mantle cell lymphoma (MCL); however, the efficacy and safety of BR is unaffected across age groups.

 

Major finding: At a median follow-up of 42 months, the elderly vs younger patient group had a significantly lower proportion of patients receiving full doses of bendamustine (54% vs 79.5%; P < .001) and higher treatment delay rate (54% vs 43.2%; P < .001) but similar disease-free survival (P = .069). The number of all-grade adverse events per patient was similar between the groups across each BR cycle.

Study details: This retrospective observational cohort study included 201 patients (elderly [≥70 years] n = 113 or younger [18-70 years] n = 88) with iNHL or MCL who received BR therapy.

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

Source: Kotchetkov R et al. Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study. Int J Cancer. 2022 (Dec 22). Doi: 10.1002/ijc.34412

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Key clinical point: In the real-world setting, dose reductions and therapy delays are more common among elderly vs younger patients receiving first-line bendamustine-rituximab (BR) for indolent non-Hodgkin's lymphoma (iNHL) or mantle cell lymphoma (MCL); however, the efficacy and safety of BR is unaffected across age groups.

 

Major finding: At a median follow-up of 42 months, the elderly vs younger patient group had a significantly lower proportion of patients receiving full doses of bendamustine (54% vs 79.5%; P < .001) and higher treatment delay rate (54% vs 43.2%; P < .001) but similar disease-free survival (P = .069). The number of all-grade adverse events per patient was similar between the groups across each BR cycle.

Study details: This retrospective observational cohort study included 201 patients (elderly [≥70 years] n = 113 or younger [18-70 years] n = 88) with iNHL or MCL who received BR therapy.

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

Source: Kotchetkov R et al. Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study. Int J Cancer. 2022 (Dec 22). Doi: 10.1002/ijc.34412

Key clinical point: In the real-world setting, dose reductions and therapy delays are more common among elderly vs younger patients receiving first-line bendamustine-rituximab (BR) for indolent non-Hodgkin's lymphoma (iNHL) or mantle cell lymphoma (MCL); however, the efficacy and safety of BR is unaffected across age groups.

 

Major finding: At a median follow-up of 42 months, the elderly vs younger patient group had a significantly lower proportion of patients receiving full doses of bendamustine (54% vs 79.5%; P < .001) and higher treatment delay rate (54% vs 43.2%; P < .001) but similar disease-free survival (P = .069). The number of all-grade adverse events per patient was similar between the groups across each BR cycle.

Study details: This retrospective observational cohort study included 201 patients (elderly [≥70 years] n = 113 or younger [18-70 years] n = 88) with iNHL or MCL who received BR therapy.

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

Source: Kotchetkov R et al. Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study. Int J Cancer. 2022 (Dec 22). Doi: 10.1002/ijc.34412

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Glofitamab induces a durable complete response in diffuse large B-cell lymphoma

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Key clinical point: Fixed-duration glofitamab treatment led to durable complete responses and a grade ≥3 adverse event (AE) rate of >50% in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

 

Major finding: At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. The median time to a complete response was 42 (95% CI 42-44) days; 78% of patients with a complete response continued to be in remission at 12 months. The grade ≥3 AE rate was 62%.

Study details: This phase 2 part of a phase 1-2 study included 155 adult patients with relapsed/refractory DLBCL previously treated with ≥2 lines of therapy who received obinutuzumab pretreatment followed by fixed-duration glofitamab monotherapy for 12 cycles.

Disclosures: This study was funded by F. Hoffmann-La Roche. Some authors reported ties with various organizations, including F. Hoffmann-La Roche. Two authors declared being employees of and holding stock or stock options in F. Hoffmann-La Roche.

Source: Dickinson MJ et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231 (Dec 11). Doi: 10.1056/NEJMoa2206913

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Key clinical point: Fixed-duration glofitamab treatment led to durable complete responses and a grade ≥3 adverse event (AE) rate of >50% in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

 

Major finding: At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. The median time to a complete response was 42 (95% CI 42-44) days; 78% of patients with a complete response continued to be in remission at 12 months. The grade ≥3 AE rate was 62%.

Study details: This phase 2 part of a phase 1-2 study included 155 adult patients with relapsed/refractory DLBCL previously treated with ≥2 lines of therapy who received obinutuzumab pretreatment followed by fixed-duration glofitamab monotherapy for 12 cycles.

Disclosures: This study was funded by F. Hoffmann-La Roche. Some authors reported ties with various organizations, including F. Hoffmann-La Roche. Two authors declared being employees of and holding stock or stock options in F. Hoffmann-La Roche.

Source: Dickinson MJ et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231 (Dec 11). Doi: 10.1056/NEJMoa2206913

Key clinical point: Fixed-duration glofitamab treatment led to durable complete responses and a grade ≥3 adverse event (AE) rate of >50% in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

 

Major finding: At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. The median time to a complete response was 42 (95% CI 42-44) days; 78% of patients with a complete response continued to be in remission at 12 months. The grade ≥3 AE rate was 62%.

Study details: This phase 2 part of a phase 1-2 study included 155 adult patients with relapsed/refractory DLBCL previously treated with ≥2 lines of therapy who received obinutuzumab pretreatment followed by fixed-duration glofitamab monotherapy for 12 cycles.

Disclosures: This study was funded by F. Hoffmann-La Roche. Some authors reported ties with various organizations, including F. Hoffmann-La Roche. Two authors declared being employees of and holding stock or stock options in F. Hoffmann-La Roche.

Source: Dickinson MJ et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231 (Dec 11). Doi: 10.1056/NEJMoa2206913

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Zanubrutinib tops ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

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Key clinical point: Compared with ibrutinib, zanubrutinib prolonged progression-free survival and demonstrated an improved safety profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

 

Major finding: At a median follow-up of 29.6 months, the zanubrutinib vs ibrutinib group had a 35% decreased risk for progression or death (hazard ratio 0.65; P = .002) and a lower incidence of cardiac disorders (21.3% vs 29.6%) and adverse events leading to treatment discontinuation (15.4% vs 22.2%).

Study details: Findings are from the multicenter phase 3 ALPINE trial including 652 adult patients with relapsed or refractory CLL/SLL treated with ≥1 previous line of therapy who were randomly assigned to receive zanubrutinib (n = 327) or ibrutinib (n = 325).

Disclosures: This study was funded by BeiGene. Some authors reported ties with various organizations, including BeiGene. Six authors declared being employees of or holding stock or stock options in BeiGene.

Source: Brown JR et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2022;388(4):319-332 (Dec 13). Doi: 10.1056/NEJMoa2211582

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Key clinical point: Compared with ibrutinib, zanubrutinib prolonged progression-free survival and demonstrated an improved safety profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

 

Major finding: At a median follow-up of 29.6 months, the zanubrutinib vs ibrutinib group had a 35% decreased risk for progression or death (hazard ratio 0.65; P = .002) and a lower incidence of cardiac disorders (21.3% vs 29.6%) and adverse events leading to treatment discontinuation (15.4% vs 22.2%).

Study details: Findings are from the multicenter phase 3 ALPINE trial including 652 adult patients with relapsed or refractory CLL/SLL treated with ≥1 previous line of therapy who were randomly assigned to receive zanubrutinib (n = 327) or ibrutinib (n = 325).

Disclosures: This study was funded by BeiGene. Some authors reported ties with various organizations, including BeiGene. Six authors declared being employees of or holding stock or stock options in BeiGene.

Source: Brown JR et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2022;388(4):319-332 (Dec 13). Doi: 10.1056/NEJMoa2211582

Key clinical point: Compared with ibrutinib, zanubrutinib prolonged progression-free survival and demonstrated an improved safety profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

 

Major finding: At a median follow-up of 29.6 months, the zanubrutinib vs ibrutinib group had a 35% decreased risk for progression or death (hazard ratio 0.65; P = .002) and a lower incidence of cardiac disorders (21.3% vs 29.6%) and adverse events leading to treatment discontinuation (15.4% vs 22.2%).

Study details: Findings are from the multicenter phase 3 ALPINE trial including 652 adult patients with relapsed or refractory CLL/SLL treated with ≥1 previous line of therapy who were randomly assigned to receive zanubrutinib (n = 327) or ibrutinib (n = 325).

Disclosures: This study was funded by BeiGene. Some authors reported ties with various organizations, including BeiGene. Six authors declared being employees of or holding stock or stock options in BeiGene.

Source: Brown JR et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2022;388(4):319-332 (Dec 13). Doi: 10.1056/NEJMoa2211582

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Mantle cell lymphoma: Long-term data support high-dose cytarabine-containing regimens

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Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

 

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O 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. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

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Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

 

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O 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. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

 

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O 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. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

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Regular laxative use tied to increased dementia risk

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Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

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Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

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