Ixazomib-Based Consolidation and Maintenance Prolongs Progression-Free Survival after Salvage Autologous Stem Cell Transplantation (sASCT): Results from Interim Analysis of UK-MRA Myeloma XII (ACCoRD)

Introduction: sASCT in multiple myeloma (MM) induces superior durability of response over non-transplant consolidation 1. Currently there is no prospective evidence for post-sASCT consolidation and maintenance. This is important given that most patients relapsing after first ASCT (ASCT1) are lenalidomide refractory (Len-Ref) following maintenance. The role of a proteasome inhibitor (PI) containing post-sASCT consolidation and maintenance strategy is explored in UK-MRA Myeloma XII (ACCoRD) trial using the second-generation oral PI, ixazomib. The results of a planned interim analysis (IA) of efficacy and safety are presented here. Patients and Methods: ACCoRD enrolled patients who relapsed, requiring treatment more than 12m after ASCT1, delivering an oral PI/IMID re-induction regimen (ixazomib, thalidomide and dexamethasone; ITD) prior to randomization between sASCT conditioned with high-dose melphalan (HDM) vs. ixazomib-augmented ( iMel). The second randomization between observation (standard of care in sASCT; OBS) and post-transplant ITD consolidation and ixazomib maintenance (CON/MAINT), was conducted at D100 post-sASCT. The primary endpoint was progression-free survival (PFS). Responses were assessed in accordance with IMWG criteria with MRD defined by the limit of the multi-parameter flow assay (65y. The median observed TTP from ASCT1 was 32m (range 2, 212), with 12.5% patients relapsing after lenalidomide maintenance (Len-Ref). The proportion of patients with an ASCT1 TTP 24m was 13.5%, 15.1% and 71.5%, respectively. Of those with complete genetic results at trial entry, 58.3% had standard risk, 31.1% had HiR and 10.7% had UHiR disease. 61.5% of patients were PI-exposed. The median time from sASCT to CON/MAINT was 4.3m (3.4, 6.7). The ORR following sASCT was 83.3%, with ³VGPR in 50.5% and MRD negative in 19.5%. Afte