Response adaptive salvage with KTd and ASCT for functional high‐risk multiple myeloma—The Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial

Summary We evaluated re‐induction incorporating carfilzomib–thalidomide–dexamethasone (KTd) and autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) refractory, or demonstrating a suboptimal response, to non‐IMID bortezomib‐based induction. KTd salvage consisted of thalidomide 100 mg daily and dexamethasone 20 mg orally combined with carfilzomib 56 mg/m 2 days 1, 2, 8, 9, 15 and 16, of each 28‐day cycle. Following four cycles, patients achieving a stringent complete response proceeded to ASCT whereas those who did not received a further two cycles then ASCT. Consolidation consisted of two cycles of KTd then Td to a total of 12 months post‐ASCT therapy. Primary end‐point was the overall response rate (ORR) with KTd prior to ASCT. Fifty patients were recruited. The ORR was 78% with EuroFlow MRD negativity of 34% in the intention‐to‐treat population and 65% in the evaluable population at 12 months post‐ASCT. With follow‐up >38 months median PFS and OS have not been reached with PFS and OS at 36 months of 64% and 80%, respectively. KTd was well tolerated with grade 3 and grade ≥4 adverse events rates of 32% and 10%, respectively. Response adaptive utilisation of KTd with ASCT is associated with both high‐quality responses and durable disease control in functional high‐risk NDMM.