Rituximab-based combination therapy in patients with Waldenström macroglobulinemia: a systematic review and meta-analysis

BACKGROUND: To evaluate the efficacy and safety of rituximab-based combination therapy for Waldenström macroglobulinemia (WM), we conducted this meta-analysis by pooling the rates of overall response, major response, complete response, and grade ≥3 hematological adverse events. METHODS AND MATERIALS: We searched for relevant studies in the databases of PubMed, Web of Science, Embase, and the Cochrane Library. The qualitative assessment of all the included articles was conducted with reference to the Newcastle–Ottawa Scale. A random-effects model was selected to perform all pooled analyses. RESULTS: We identified altogether 22 studies with a total of 806 symptomatic WM patients enrolled. The pooled analysis indicated that the rituximab-based combination therapy achieved an overall response rate (ORR) of 84% (95% CI: 81%–87%), a major response rate (MRR) of 71% (95% CI: 66%–75%), and a complete response rate (CRR) of 7% (95% CI: 5%–10%). Rituximab plus conventional alkylating agents–containing chemotherapy (subgroup A) yielded an ORR of 86% (95% CI: 81%–89%), an MRR of 74% (95% CI: 69%–79%), and a CRR of 8% (95% CI: 4%–14%). Rituximab plus purine analog (subgroup B) resulted in an ORR of 85% (95% CI: 79%–89%), an MRR of 74% (95% CI: 66%–81%), and a CRR of 9% (95% CI: 4%–15%). Rituximab plus proteasome inhibitor (subgroup C) resulted in an ORR of 86% (95% CI: 81%–90%), an MRR of 68% (95% CI: 58%–77%), and a CRR of 7% (95% CI: 3%–11%). Rituximab plus immunomodulatory drug (subgroup D) attained relatively lower response rates, with an ORR of 67% (95% CI: 51%–81%), an MRR of 56% (95% CI: 27%–83%), and a CRR of 5% (95% CI: 1%–12%). Common grade ≥3 hematological adverse events consisted of neutropenia (33%, 95% CI: 17%–52%), thrombocytopenia (7%, 95% CI: 3%–11%), and anemia (5%, 95% CI: 3%–9%). CONCLUSION: Rituximab in combination with an alkylating agent, purine analog, or proteasome inhibitor is highly effective with tolerable hematological toxicities for WM.