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. 2025 Mar 11;9(5):1132-1136.
doi: 10.1182/bloodadvances.2024015285.

Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma

Johannes M Waldschmidt  1   2   3   4 , Noori Sotudeh  1   2   3 , Sankalp Arora  5   6 , Tushara Vijaykumar  1   2 , Praveen Anand  1   2   3 , Hannah Stuart  1   2   3 , Julia Frede  1   2   3 , Tim Campbell  7 , Shari M Kaiser  7 , Xirong Zheng  7 , Nikhil C Munshi  1   2 , Kenneth C Anderson  1   2 , Hermann Einsele  4 , Andrew J Yee  5 , Birgit Knoechel  2   3   8 , Jens G Lohr  1   2   3 , Noopur S Raje  2   5
Affiliations

Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma

Johannes M Waldschmidt et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: J.M.W. has served as a consultant for Johnson & Johnson, Sanofi, Takeda, Pfizer, Oncopeptides, and Skyline Dx; received honoraria from Takeda, GlaxoSmithKline (GSK), PharmaMar, and BeiGene; and has received research support from Bristol Myers Squibb (BMS). T.C., S.M.K., and X.Z. are current or past employees of BMS. K.C.A. has consulted for Johnson & Johnson, Pfizer, and AstraZeneca, and is a founder and/or board member of C4 Therapeutics, Starton, Window, Dynamic Cell Therapies, and Predicta Biosciences. H.E. has consulted for BMS, Johnson & Johnson, Amgen, Takeda, Sanofi, GSK, and Novartis; discloses research funding from BMS, Johnson & Johnson, Amgen, GSK, and Sanofi; has received honoraria from BMS, Johnson & Johnson, Amgen, Takeda, Sanofi, GSK, and Novartis; and received travel support from BMS, Johnson & Johnson, Amgen, Takeda, Novartis, and Sanofi. A.J.Y. has consulted for AbbVie, Adaptive Biotechnologies, Amgen, BMS, Celgene, GSK, Johnson & Johnson, Karyopharm, Oncopeptides, Pfizer, Prothena, Regeneron, Sanofi, Sebia, and Takeda, and has received research funding to institution from Amgen, BMS, GSK, Johnson & Johnson, and Sanofi. N.S.R. has consulted for Amgen, BMS, Johnson & Johnson, Sanofi, Takeda, AstraZeneca, and C4 Therapeutics; has participated in advisory boards for Caribou and Immuneel; and received research funding from bluebird bio. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Nivolumab to salvage T-cell fitness in CAR-T refractory MM. (A) The serologic response to ide-cel and nivolumab-based salvage therapy in MM1 (left panel) and MM2 (right panel). (B) CAR-T vector expansion over time indicating the time of first and second ide-cel infusion. (C) Study design for correlative T-cell assessment. (D) A tSNE plot of single CD3+ non–CAR-Ts, showing 3 distinct clusters relating to treatment with nivolumab-based salvage therapy. (E) The heat map in panel E visualizes cluster characterization by marker gene expression for clusters 1, 2, and 3. (F) Gene set enrichment plots show expressed gene sets derived from the BIOCARTA T helper 1 cells/T helper 2 cells and BIOCARTA natural killer T cell pathway in MM1 (cluster 3 vs 1) and MM2 (cluster 3 vs 2). DRd, daratumumab-lenalidomide-dexamethasone; FDR, false discovery rate; FLC, free light chain; KCd, carfilzomib-cyclophosphamide(-dexamethasone); NES, normalized enrichment score; Nivo, nivolumab; Pd, pomalidomide-dexamethasone; pts, patients; Rd, lenalidomide-dexamethasone; sFLC, serum-free light chain; tSNE, t-stochastic network embedding. Figure panel C created with BioRender (https://BioRender.com/i46u828#).
See this image and copyright information in PMC

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