P-076: Early free light-chain suppression after CAR-T therapy is predictive for progression-free and overall survival

Introduction: CAR-T cells directed against BCMA have demonstrated remarkable efficacy and were recently approved by FDA and EMA for second or third line therapy. Only a minority of patients are primary refractory to CAR-T cells, however early relapse remains a challenge and is correlated with poor overall survival. Recently the MyCARe score has been proposed to predict PFS and OS based on the presence of extramedullary disease, plasma cell leukemia, high-risk cytogenetics, elevated ferritin and lenalidomide-refractoriness. While the number of these risk factors clearly predicted inferior PFS and OS after CAR-T therapy, it will be difficult to withhold CAR-T cells from patients with high MyCARe scores, since they have the highest medical need and most likely the worst outcome with any alternative therapy. Another option to address early treatment failure after CAR-T would be to define a biomarker for progression very early after CAR-T treatment.

Methods: Patients with myeloma and treatment with commercial CAR-T cells at a large academic institution from 1/2022 to 12/2023 were analyzed for PFS and OS. Minimum follow up was 3 months. Free light-chain (FLC) suppression was assessed on day 28 after CAR-T infusion and defined as undetectable serum levels of both FLC kappa and lambda. FLC suppression was tested as biomarker to predict PFS and OS after CAR-T therapy.

Results: 43 patients received either ide-cel (n= 22) or cilta-cel (n=21) as standard therapy for relapsed/refractory myeloma. Median follow up was 9.8 (range 3-32) months and median PFS was 11.5 (range 6.3-16.7) months. Twenty-nine patients showed FLC suppression on day 28 and 11 have progressed so far, showing a median PFS of 14.5 (range 10.9-18.1) months and an OS of 88,1% at 12 months (median not reached). In contrast, of the 14 patients with no FLC suppression on day 28 after CAR-T infusion, 12 progressed with a median PFS of 2.3 (range 0.2-4.3) months and a median OS of 12.7 (3,73-21,6) months. By log rank test achieving FLC suppression was significant for PFS (log-rank p< 0.001) and OS (p=0.002).

Conclusions: Based on our results the failure to achieve FLC suppression on day 28 after CAR-T therapy is highly predictive for a markedly inferior PFS and OS. This simple biomarker could help to identify patients with a suboptimal early response and a high risk of dying within 12 months. These patients may benefit from early additional intervention with agents such as bi-specific antibodies, IMIDs or CELMODs.