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

Abstract

SummaryThe growing use of frontline lenalidomide treatment in multiple myeloma (MM) is increasing the proportion of lenalidomide‐refractory patients, which may limit the efficacy of subsequent lines of treatment (LOT). This systematic literature review (January 2008–October 2023) of clinical trials (CT) and real‐world studies (RW) assessed treatment outcomes in adults with relapsed/refractory MM (RRMM) who were previously treated with ≥1 LOT, progressed and were lenalidomide‐refractory. Medline, EMBASE and additional electronic databases were searched for articles published in English. Primary outcomes included progression‐free survival (PFS), overall survival (OS) and overall/objective response rate (ORR); 24 CT and 19 RW were included. For CT, the population‐weighted mean of median PFS (CT = 14) and OS (CT = 6) were shorter in the lenalidomide‐refractory cohort (months: 8.8 [n = 2699] and 21.7 [n = 1066], respectively) than the intent‐to‐treat population (months: 13.8 [n = 5380] and 35.9 [n = 2264], respectively); the population‐weighted (N = 2142) mean ORR for lenalidomide‐refractory patients (CT = 18) was 56.0%. RW reported considerable variation in PFS (RW = 7), OS (RW = 8) and ORR (RW = 8); and median PFS (RW = 2; months) was lower in lenalidomide/bortezomib‐refractory (5.5/5.5; n = 81/n = 25) versus lenalidomide‐refractory (7.3/8.0; n = 81/n = 61) patients. These data provide evidence that clinical trials and real‐world outcomes are suboptimal in lenalidomide‐refractory patients with RRMM, highlighting the need to improve treatment options for this population.