Reporting of Postprotocol Therapies and Attrition in Multiple Myeloma Randomized Clinical Trials A Systematic Review

This systematic review examines the reporting of postprotocol treatment received by patients enrolled in randomized clinical trials for new-onset or relapsed/refractory multiple myeloma. Question What proportion of multiple myeloma randomized clinical trials report postprotocol therapies, and when reported, how do these therapies compare with existing standard of care? Findings In this systematic review of 103 randomized clinical trials including 47 251 patients, only 43.7% of the trials reported postprotocol therapies. When described, the proportion of patients receiving postprotocol therapies was low, and often not at par with standard of care therapy. Meaning These findings suggest that reporting of postprotocol therapies is poor in multiple myeloma trials, necessitating reporting guidelines on postprotocol therapies for ongoing and future trials. Importance A thorough understanding of the optimal role and sequence of agents for treatment of multiple myeloma (MM) requires knowledge of the use and rate of postprotocol therapies in randomized clinical trials (RCTs). Objectives To examine the proportion of MM RCTs that reported postprotocol therapies and, among those, the percentage of patients who received no further therapy and how treatments differed between the control and intervention arms. Evidence Review The reporting of postprotocol therapies was systematically assessed in published MM RCTs using 3 databases (PubMed, Embase, and Cochrane Registry of Controlled Trials) for MM RCTs from January 1, 2005, to December 30, 2019. All MM RCTs were included, and all other studies, such as editorials, nonrandomized studies, and review articles, were excluded. Findings A total of 103 RCTs were identified (47 251 patients); of these, 45 (43.7%) reported subsequent treatments in that publication or in any subsequent publication. Trials funded by pharmaceutical companies (26 of 47 [55.3%]) were more likely to report subsequent treatments than cooperative group studies (19 of 56 [33.9%]) (chi(2)(1,103) = 4.8; P = .03). Differences were found in the treatments received between the intervention and control arms of RCTs. When data were reported, 5150 of 9351 patients (54.9%) in RCTs of newly diagnosed MM and 2197 of 4501 patients (48.8%) in RCTs of relapsed/refractory MM received any subsequent therapy. Conclusions and Relevance Postprotocol therapies in MM RCTs are often not reported and, when they are, many patients receive no further therapy. Reporting guidelines for postprotocol therapies are needed.

Automated summary

This systematic review found that less than half of multiple myeloma randomized clinical trials reported postprotocol therapies, with a low proportion of patients receiving these therapies, often not meeting the standard of care. Reporting guidelines for postprotocol therapies are urgently needed to improve the reporting quality in ongoing and future trials.