A systematic review of comparative schedule-related toxicities with maintenance rituximab in follicular and mantle cell lymphomas

Abstract

We conducted a systematic review of grade 3/4 adverse events (AEs) reported in prospective trials enrolling patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) receiving maintenance rituximab (MR). Random-effects models were used to calculate summary estimates and 95% confidence intervals for the proportion of AEs occurring during MR. Differences by induction program, histology, setting and MR schedule were examined by stratified analyses and univariate random-effects meta-regression. Eleven trials met the search criteria, with nine sufficiently reporting AEs during the MR phase. Of 1009 patients receiving MR, the proportion experiencing cumulative grade 3/4 toxicity was 24% (95% confidence interval [CI]: 14-36%). Patients receiving MR every 6 months as four weekly infusions for 2 years had significantly less toxicity compared with those receiving MR every 2 months (10% vs. 28%; p = 0.035). Patients treated with rituximab alone during induction had fewer toxicities compared to those treated with rituximab plus chemotherapy induction (12% vs. 35%; p = 0.031). Myelosuppression and infections were the most common toxicities. Our literature analysis suggests that MR given every 6 months and rituximab alone as induction may be associated with fewer grade 3/4 AEs for patients with FL and MCL; however, assessing the true independent impact of induction regimens and schedule on toxicity will require prospective trials.

Chronic Benign CD8+ Proliferation: A Rare Affection that Can Mimic a Lymphoma Relapse

“…In certain cases, especially in repeated doses, it causes clinically apparent immunodeficiency. Infections and neutropenia, usually combined with severe hypogammaglobulinemia, are the most common long-term side effects [12–14].…”

Rituximab Maintenance Strategy in Advanced Follicular Lymphoma: Facts and Controversies

“…In a systematic review of rituximab maintenance therapy that included 11 clinical trials and 1009 patients suff ering from FL or MCL, suppression of bone marrow and infections were most common toxicities, with 24% of patients experiencing grade 3 or 4 toxicity 51 . Signifi cantly less toxicity was found in the regimen of 4 weekly rituximab infusions every 6 months compared to PRIMA schedule (once in two months for 2 years), i.e.…”

Too much and not enough: revisiting maintenance rituximab in indolent lymphomas

“… 1 , 2 Although none of these schedules has been directly compared, small retrospective reviews suggest relative equivalence in terms of efficacy and small differences in terms of toxicity. 3 In frontline follicular lymphoma, the PRIMA trial established one dose of maintenance rituximab every 8 weeks based on achieving a trough level of 25 mg/mL in the majority of patients, and this has arguably become the most common schedule. 4 It is important to note that there remains a lack of a survival advantage for maintenance rituximab in frontline follicular lymphoma, but 10-year data show impressive and persistent disease control and validate maintenance rituximab for 2 years as an appropriate option to improve progression- free survival in patients with high-tumor burden follicular lymphoma.…”