Outcomes in randomized controlled trials of therapeutic interventions for multiple myeloma: A systematic review

Many clinical trials of therapeutic interventions for multiple myeloma do not use patient important outcomes and rely on the use of surrogate endpoints. The aim of this systematic review was to depict the landscape of randomized controlled trials in myeloma research and compile the endpoints utilized.

We searched Embase, PubMed, and the Cochrane Library for randomized controlled trials in myeloma published in English up to October 2023. We included trials exploring efficacy of therapeutic modalities for myeloma itself or supportive care interventions.

A total of 2181 records, reporting data from 624 trials (448 comparing anti-myeloma treatments and 176 comparing supportive interventions) were deemed eligible. The most common primary outcome reported was disease response, followed by progression free survival (PFS) and overall survival (OS). Across all trials, 119 (19.1 %) used OS as the primary endpoint, while 316 (50.6 %) listed it as a secondary endpoint. Quality of life was less commonly prioritized, featured as primary endpoint only in seven studies (1.1 %) and as secondary endpoint in 115 studies (18.4 %). Studies funded by the pharmaceutical industry were more likely (Odds Ratio [OR] 3.85, 95 % CI 2.41-6.35) to use PFS as primary outcome. Similarly, studies with authors that had conflicts of interest with the funding source were more likely (OR 4.57, 95 % CI 2.72-7.92) to use PFS as the primary outcome.

While randomized controlled trials for multiple myeloma predominantly rely on surrogate endpoints, particularly PFS, the importance of OS as an outcome should not be overlooked.