Scientific publications

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

Sep 1, 2023 | Magazine: Blood Cancer Discovery

Bruno Paiva  1 , Irene Manrique  1 , Julie Rytlewski  2 , Timothy Campbell  3 , Christian C Kazanecki  2 , Nathan Martin  2 , Larry D Anderson Jr.  4 , Jesús G Berdeja  5 , Sagar Lonial  6 , Noopur S Raje  7 , Yi Lin  8 , Philippe Moreau  9 , Jesús F San-Miguel  1 , Nikhil C Munshi  10 , Shari M Kaiser  2


Abstract

The role of measurable residual disease (MRD) in multiple myeloma patients treated with chimeric antigen receptor (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) versus 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 versus <CR. Persistent MRD in the 10-6 logarithmic range and reappearance of normal plasma cells in MRD-negative patients were associated with inferior PFS. This study unveils different prognostic implications of serological and MRD response dynamics after ide-cel and suggests the potential value of studying the reappearance of normal plasma cells as a surrogate of loss of CAR T-cell functionality.

Significance: This is one of the first studies evaluating the impact of CR and MRD dynamics after CAR T therapy in relapsed/refractory multiple myeloma. These data help interpret the prognostic significance of serological and MRD responses at early and late time points after CAR T-cell infusion. See related commentary by Landgren and Kazandjian, p. 346 . This article is featured in Selected Articles from This Issue, p. 337.

CITATION  Blood Cancer Discov. 2023 Sep 1;4(5):365-373.  doi: 10.1158/2643-3230.BCD-23-0044

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