Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel

Abstract

The role of MRD in multiple myeloma patients treated with CAR T cells is uncertain. We analyzed MRD kinetics during the first year after idecabtagene vicleucel (ide-cel) infusion in 125 relapsed/refractory multiple myeloma patients enrolled in KarMMa. At month 1 after ide-cel, there were no differences in progression-free survival (PFS) between patients in less than complete response (CR) vs those in CR; only MRD status was predictive of significantly different PFS at this landmark. In patients with undetectable MRD at 3 months and beyond, PFS was longer in those achieving CR vs <CR. Persistent MRD in the 10-6 logarithmic range and reappearance of normal plasma cells in MRD negative patients associated with inferior PFS. This study unveiled different prognostic implications of serological and MRD response dynamics after ide-cel and suggests potential value of studying the reappearance of normal plasma cells as a surrogate of loss of CAR T cell functionality.

Immune status and selection of patients for immunotherapy in myeloma: a proposal

“…Early eradication of residual disease may be critical to achieving cures in this group. 77 Tumors earlier in the course of evolution to MM may also fall into this group 18 and may provide the rationale for the consideration of T-cell redirection in earlier stages of MM development, if safety could be ensured.…”

Role of minimal residual disease assessment in multiple myeloma

“…Therefore, the role of MRD evaluation in the context of these novel therapies remains to be fully validated. 78 …”

“… 86 Finally, discordant MRD and IF results are frequently observed after CAR T-cell therapy, with low rates of CR observed in patients achieving MRD negativity, particularly in the first six months after treatment, suggesting that MRD evaluation which reflects the clearance of myeloma cells in the BM could be an independent prognostic marker in that setting. 78 Therefore, assessing MRD in patients achieving at least VGPR or better is very relevant and informative.…”