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

Abstract

<h3>Background</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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). <h3>Conclusion</h3> 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.