Immune Engager Therapies Are Associated with Better Outcomes in Post Ide-Cel Relapse in MM- an Analysis of the US MM Immunotherapy Consortium Database.

Outcomes after CART cell therapy in myeloma is not well known in the literature and the question of whether subsequent immune engager therapies (IET) are efficacious due to T cell exhaustion also remain. Hence, we examined the outcomes of patients post ide-cel, and characterized relapses, therapies, and Progression free survival (PFS) PFS-1, PFS-2 in a real-world setting.Methods: This was a retrospective multicenter observational study of patients who underwent treatment for relapsed Multiple myeloma (MM) with ide-cel from 11 US medical centers. Each center obtained independent institutional review board approval and informed consent per institutional requirements. Only patients who relapsed post ide-cel therapy were included. Subsequent lines of therapy, patterns of relapse and response outcomes were recorded. Kaplan-Meier survival curves were used to estimate OS, PFS, and DOR, and the log-rank test was used to compare survival among groups.Results: A total of 145 patients relapsed after ide-cel were included in this analysis. Prior to ide-cel the median age was 64 yrs., with a median of 6 lines of therapy and Extramedullary disease (EMD) was present in 44% of patients. Flu/Cy was the predominant regimen used for lymphodepletion and 55%, 45% of patients had VGPR or better at 3 and 6 months. The median PFS in MM in this cohort with documented relapses was 150.5 days.In 1st relapse post ide-cel the mean M spike was 0.21 mg and median involved light chains was 124 mg/l at relapse. 57% of patients had Extra or Paramedullary disease (EMD/PMD) on relapse. The predominant subsequent therapy was non cytotoxic (ex-Dara, Selinexor) -33%, followed by IET-29%, targeted therapy at 5.6%, cytotoxic chemo at 15% and XRT only in 4.9%. BCMA Bispecific was the predominant subsequent IET used at 65% followed by belantamab at 20%. ORR was 24.9% and the median PFS was 60 days.In 2nd relapse, 63 patients were included, 43% of patients had EMD/ PMD on relapse The predominant subsequent therapy was non cytotoxic -43%, followed by IET-30% and cytotoxic chemo at 24%. The ORR was 26.9% and the median PFS was 47 days.In 1st relapse the ORR for IEC was 38% while for non-IEC therapy is 22.3% (p=0.1) while the median PFS was 106 vs 66 days (p=0.004). In 2nd relapse post CART, the ORR for IEC was 21% and for non-IEC therapy is 29.5% (p=0.69) while the median PFS was 66 vs 44 days (p=0.3).Conclusions: In this large retrospective multicenter cohort looking at post relapse outcomes of ide-cel, the median PFS 1 and PFS 2 was 60 and 47 days. IEC therapies were associated with better median PFS even immediately after ide-cel therapy and should be considered as the first choice if available.