Selinexor plus lenalidomide versus lenalidomide alone as maintenance therapy after autologous haematopoietic stem cell transplantation in newly diagnosed multiple myeloma: Results of the phase 3 ALLG MM23 (SeaLAND) trial.

SeaLAND (ALLG MM23, ACTRN12620000291987) was a randomized, open-label phase III study evaluating low-dose weekly selinexor (40 mg) plus lenalidomide (selinexor-R) versus lenalidomide alone (R) as post-transplant maintenance therapy for newly diagnosed, transplant-eligible multiple myeloma. A total of 142 patients were enrolled (R = 64; selinexor-R = 78); the trial closed early for futility. At best response, the complete response (≥CR) rate was numerically, but not significantly, higher with selinexor-R than R (67% vs. 53%, p = 0.09). At 24 months median follow-up, progression-free survival (PFS) was not significantly different between selinexor-R compared to R (hazard ratio [HR] = 1.22; 95% confidence interval [CI] 0.62-2.41; p = 0.56); 24-month PFS rates were 73% (95% CI 57%-84%) for R and 70% (95% CI: 56%-81%) for selinexor-R. The mean relative dose intensity (RDI) of R was lower in the selinexor-R arm compared to R alone (68% vs. 81%, p = 0.002); the mean RDI of S was 55%. Grade ≥3 adverse events were more frequent with selinexor-R (85% vs. 45%, p < 0.001). Common severe non-haematological adverse events included infections (R: 6%, selinexor-R: 19%, p < 0.01) and gastrointestinal disorders (R: 3%, selinexor-R: 14%, p < 0.05). Selinexor-R maintenance did not improve PFS and substantially increased toxicity. Selinexor-R maintenance cannot be recommended for the general myeloma population; we did not observe a benefit among high-risk disease.