Efficacy of interventions for newly diagnosed multiple myeloma: An umbrella review

Purpose: Many systematic reviews have examined treatment efficacy for newly diagnosed multiple myeloma (NDMM). We performed an umbrella review of these systematic reviews to provide a comprehensive examination of the current body of evidence, aiming to scope current review-level evidence and identify weaknesses in these reviews.

Methods: We identified systematic reviews examining efficacy of NDMM interventions in multiple databases published from January 1, 1990 through July 10, 2023. We explored potentially concerning issues which may compromise the validity of the conclusions in these reviews. We assessed the reviews’ quality, summarized the findings, and present potential evidence gaps.

Results: Eighty-seven reviews on NDMM treatment were included. Only seven assessed the strength of evidence. Treatments strategies like bortezomib-based induction for transplant-eligible patients, daratumumab for transplant-ineligible patients, and lenalidomide maintenance had moderate to high evidence. No reviews evaluated chimeric antigen receptor T-cell therapy or bispecific antibodies for NDMM. We identified five concerning issues: 1) inappropriate data abstraction (N=6), 2) inappropriate meta-analytic approaches (N=5), 3) not accounting for different induction strategies when evaluating the efficacy of consolidation/maintenance therapies (N=9), 4) implicit assumption that treatment efficacy is similar between transplant eligible and ineligible patients (N=13), and 5) inappropriate study selection (including observational studies or single-arm trials for treatment efficacy evaluation, which may lead to substantial biases; N=17).

Conclusion: This umbrella review provided a contemporary analysis of treatment efficacy for NDMM. We identified several weaknesses in existing reviews, indicating additional scrutiny of publishing systematic reviews in MM is warranted.