P-188: Carfilzomib, lenalidomide, and dexamethasone followed by salvage autologous stem cell transplant with or without maintenance for relapsed or refractory multiple myeloma

Background Salvage high dose chemotherapy followed by autologous stem cell transplantation (HDCT/ASCT) is a treatment option in patients with relapsed and/or refractory multiple myeloma (RRMM) after prolonged remissions with frontline transplantation. The role of salvage HDCT/ASCT following re-induction treatment with state-of-the-art triplet regimens has not been defined. The present analysis therefore aims to investigate the efficacy and toxicity of salvage HDCT/ASCT after carfilzomib (CFZ)/lenalidomide (LEN)/dexamethasone (KRd) re-induction with or without post-transplant maintenance treatment. Methods We retrospectively assessed efficacy and toxicity in 44 patients receiving salvage HDCT/ASCT following re-induction with carfilzomib/lenalidomide/dexamethasone (KRd). All patients had received frontline HDCT/ASCT with median time to progression (TTP1) of 2.9 (1.2-13.5) years, allowing for paired comparison of frontline and salvage HDCT/ASCT. Median age at time of re-induction was 58.9 years (range 40-71) and n=38/44 patients (86%) had only 1 prior line of therapy (range 1-3). Sixteen of 44 patients (36%) were LEN pretreated and all patients were CFZ-naive. Maintenance treatment was administered in n=22/44 patients (50%) after frontline HDCT/ASCT and in n=17/44 patients (39%) after salvage HDCT/ASCT. Results After a median of 3 re-induction cycles (range 3-9), 25/44 patients (57%) attained at least very good partial response (VGPR), which increased to 34/44 (77%) at best response after salvage HDCT/ASCT. Patients achieving deep remissions during frontline treatment were more likely to re-achieve deep remissions in the salvage setting at each individual timepoint: after (re-)induction (≥VGPR: odds ratio [OR] 6.22; 95% confidence interval [95%-CI] 1.33-29.01; p=0.02), after (salvage) HDCT/ASCT (≥nCR: OR 5.71; 95%-CI 1.44-22.62; p=0.01) and at best response (≥nCR: OR 4.50; 95%-CI 1.12-18.13; p=0.03). After a median follow up of 23.9 months, median progression-free survival (PFS) was 23.3 months from salvage HDCT/ASCT. Patients at least in VGPR at the time of salvage HDCT/ASCT and those receiving maintenance treatment post salvage HDCT/ASCT had significantly superior PFS (hazard ratio [HR] 0.19, p=0.001 and HR 0.20, p=0.009). In patients achieving at least an equal depth of response before salvage HDCT/ASCT as before frontline HDCT/ASCT, PFS after salvage HDCT/ASCT was comparable to the frontline situation (p=0.3). Conclusion Despite higher comorbidity scores at salvage HDCT/ASCT, no significant increase in relevant toxicity parameters including infections and intensive care unit admission was observed and no transplant-related mortality occurred after salvage HDCT/ASCT. This is the first report of state-of-the-art triplet re-induction and salvage HDCT/ASCT for RRMM after frontline transplantation. Deep remissions achieved with KRd translate into prolonged PFS following salvage HDCT/ASCT and are enhanced by maintenance treatment.