Study Identifies Lenalidomide-Carfilzomib as Best Maintenance Treatment Option in MM

Novel agents and combination treatment regimens have advanced the treatment of multiple myeloma (MM) in recent decades, but identifying the best maintenance treatment regimen has proven challenging. A recent review and analysis published in the journal Hematology suggests that lenalidomide-carfilzomib is the most effective option, although further studies are necessary to confirm.

“Despite advances in novel agents, the relapse and progression of MM were still inevitable after induction and consolidation treatment,” the authors wrote. “Therefore, to conquer this dilemma, literally to prolong the long-term survival of MM patients, maintenance therapies presumably enhancing the response of initial treatment have been proposed and widely investigated.”

Several maintenance therapy strategies have been studied in recent decades, but many came with significant toxicity that outweighed their efficacy. The immunomodulatory drug lenalidomide was established as an effective option and became the MM maintenance treatment standard in 2005. More recently, the proteasome inhibitors bortezomib, carfilzomib, and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab have expanded the therapy armamentarium.

Despite a growing roster of treatment options, a lack of direct comparisons between the various drug options makes it difficult for clinicians to choose the best treatment strategy. The review authors aimed to provide clarity on the most appropriate treatment options by also conducting a network meta-analysis to form indirect comparisons between regimens.

The analysis included a total of 19 trials encompassing 8337 patients with newly diagnosed MM and 11 maintenance therapy options. The main end point was overall survival (OS), and odds ratios (ORs) were generated for dichotomous variants. Progression-free survival (PFS) was also assessed.

Lenalidomide and daratumumab were each significantly more effective than a placebo when it came to OS, with OR ranges of 1.61 to 1.9 and 1.83 to 2.41, respectively. Where PFS is concerned, combination lenalidomide-carfilzomib, combination lenalidomide-prednisone, combination bortezomib-thalidomide, daratumumab, lenalidomide, ixazomib, and thalidomide all were effective vs a placebo.

Within the group of therapies showing efficacy over a placebo, lenalidomide-carfilzomib was a standout against the rest of the group, including lenalidomide, daratumumab, and ixazomib. Overall, considering both OS and PFS, lenalidomide plus carfilzomib was the authors’ recommended maintenance therapy option. However, they note that further head-to-head studies could help confirm its superiority over other therapies. This regimen also carries a risk of adverse events as well as a financial burden that clinicians should consider.

Limitations of the study included potential missed literature, the study’s analysis of PFS and OS alone, and the limited number of studies overall—particularly for newer regimens.

“In conclusion, post-autologous stem cell transplantation maintenance therapy with lenalidomide continued is the current standard of care based on the available clinical trial data, the most likely next step will be to incorporate carfilzomib into the maintenance setting,” the authors wrote.

“Physicians also need to be vigilant about the risk of adverse event and cost-economic in MM patients treated with lenalidomide-carfilzomib. More head-to-head clinical trials are needed to confirm our findings.”

Reference

Zhi Y, Bao S, Mao J, et al. Efficacy of maintenance treatment in patients with multiple myeloma: a systematic review and network meta-analysis. Hematology. Published online September 20, 2022. doi:10.1080/16078454.2022.2121900