Impact of prior lenalidomide or proteasome inhibitor exposure on the effectiveness of ixazomib–lenalidomide–dexamethasone for relapsed/refractory multiple myeloma: A pooled analysis from the INSURE study

AbstractObjectivesTo characterize the impact of prior exposure and refractoriness to lenalidomide or proteasome inhibitors (PIs) on the effectiveness and safety of ixazomib–lenalidomide–dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM).MethodsINSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA‐IXA, and REMIX.ResultsOverall, 391/100/68 were lenalidomide‐naïve/−exposed/−refractory and 37/411/110 were PI‐naïve/−exposed/−refractory. Median duration of therapy (DOT) was 15.3/15.6/4.7 months and median progression‐free survival (PFS) was 21.6/25.8/5.6 months in lenalidomide‐naïve/exposed/refractory patients. Median DOT and PFS in PI‐naïve/exposed/refractory patients were 20.4/15.2/6.9 months and not reached/19.8/11.4 months, respectively. The proportion of lenalidomide‐naïve/exposed/refractory patients in INSIGHT and UVEA‐IXA who discontinued a study drug due to adverse events (AEs) was ixazomib, 31.6/28.2/28.0% and 18.6/6.7/10.5%; lenalidomide, 21.9/28.2/16.0% and 16.1/6.7/10.5%; dexamethasone, 18.4/20.5/16.0% and 10.6/0/10.5%, respectively. The proportion of PI‐naïve/exposed/refractory patients in INSIGHT and UVEA‐IXA who discontinued a study drug due to AEs was: ixazomib, 44.4/28.8/27.8% and 22.2/16.7/15.7%; lenalidomide, 33.3/22.0/19.4% and 16.7/15.9/11.8%; dexamethasone, 33.3/17.4/16.7% and 16.7/9.5/7.8%, respectively. REMIX AE discontinuation rates were unavailable.ConclusionIRd appeared to be effective in RRMM patients in routine clinical practice regardless of prior lenalidomide or PI exposure, with better outcomes seen in lenalidomide‐ and/or PI‐nonrefractory versus refractory patients.