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Research in Review

Meta-Analysis Reveals Optimal Combination Therapy for Multiple Myeloma

A triple-combination treatment strategy is the most effective therapy for patients with relapsed or refractory multiple myeloma, according to a meta-analysis published in the Journal of Clinical Oncology (published online February 27, 2017; doi:10.1200/JCO.2016.71.1663).

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Many new treatment options for patients with relapsed or refractory multiple myeloma have become available since 2000. Aside from the standard of care treatments melphalan and dexamethasone, the immunomodulatory agent thalidomide and bortezomib, along with 8 other agents, have been US Food and Drug Administration approved. However, direct comparisons of these novel treatments are lacking, including a lack of direct comparisons among different treatment classes.

Chrissy H Y van Beurden-Tan, MSc, Erasmus Medical Center (Rotterdam, the Netherlands), and colleagues sought to synthesize all efficacy evidence available on these novel treatments and compare them to determine optimal treatment strategies. Researchers performed a systemic literature review of 17 randomized controlled trials including 18 treatment options. The data were synthesized using a conventional network meta-analysis.

Results of the review found the treatment combination of daratumumab, lenalidomide, and dexamethasone as most favorable in terms of a hazard ratio for progression-free survival (0.13; 95% CI, 0.09-0.19). This triple combination reduced risk of progression or treatment-related mortality by 87% versus dexamethasone alone, 81% versus bortezomib plus dexamethasone, and 63% versus lenalidomide plus dexamethasone.

Researchers reported that 13 other drug combinations had hazard ratios ranging from 0.24 (carfilzomib/lenalidomide/dexamethasone) to 0.76 (thalidomide/dexamethasone). The top 3 optimal treatment options were triple-combination regimens involving lenalidomide and dexamethasone. Double-combination regimens ranked near the bottom of the list in terms of efficacy.

Data involving adverse events and quality of life were not assessed. Overall survival hazard ratios for a majority of the reviewed trials are still immature.

Although the results of the review provide caregivers advice for appropriate treatment options for patients with relapsed or refractory multiple myeloma, researchers noted in an interview with Cancer Therapy Advisor that “selecting the most appropriate treatment option also depends on individual patient characteristics and individual preferences” (March 17, 2017). – Zachary Bessette

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