Multiple myeloma refractory to lenalidomide: A systematic literature review of trials and real-world evidence

Area of Science:

• Hematology
• Oncology
• Clinical Trials & Real-World Evidence

Background:

• Frontline lenalidomide treatment is increasingly used for multiple myeloma (MM).
• This leads to a growing proportion of lenalidomide-refractory patients, potentially limiting subsequent treatment efficacy.
• Relapsed/refractory multiple myeloma (RRMM) patients who are lenalidomide-refractory face suboptimal outcomes.

Purpose of the Study:

• To systematically review treatment outcomes in adults with RRMM who were lenalidomide-refractory.
• To assess progression-free survival (PFS), overall survival (OS), and overall/objective response rate (ORR).
• To compare outcomes from clinical trials (CT) and real-world (RW) studies.

Main Methods:

• Systematic literature review of clinical trials and real-world studies (January 2008-October 2023).
• Searched Medline, EMBASE, and other electronic databases for English-language articles.
• Included 24 CT and 19 RW studies, focusing on patients previously treated, progressed, and lenalidomide-refractory.

Main Results:

• In CT, lenalidomide-refractory patients had shorter median PFS (8.8 months) and OS (21.7 months) compared to the overall intent-to-treat population.
• The population-weighted mean ORR for lenalidomide-refractory patients in CT was 56.0%.
• RW studies showed considerable variation, with some lenalidomide/bortezomib-refractory patients experiencing even shorter PFS (5.5 months).

Conclusions:

• Both clinical trial and real-world outcomes are suboptimal for lenalidomide-refractory RRMM patients.
• Existing treatment options are insufficient for this growing patient population.
• There is a critical need to develop and implement improved therapeutic strategies for lenalidomide-refractory MM.