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Multicenter Study
. 2024 Aug 13;8(15):3859-3869.
doi: 10.1182/bloodadvances.2023012470.

Absolute lymphocyte count after BCMA CAR-T therapy is a predictor of response and outcomes in relapsed multiple myeloma

Mateo Mejia Saldarriaga  1 , Darren Pan  2 , Caitlin Unkenholz  1 , Tarek H Mouhieddine  2 , Juan Esteban Velez-Hernandez  1   3 , Katherine Engles  2 , Joshua A Fein  1 , Jorge Monge  1 , Cara Rosenbaum  1 , Roger Pearse  1 , David Jayabalan  3 , Christian Gordillo  4 , Hei Ton Chan  4 , Samuel Yamshon  1 , Santiago Thibaud  2 , Markus Mapara  4 , Giorgio Inghirami  5 , Suzanne Lentzsch  4 , Ran Reshef  4 , Adriana Rossi  2 , Samir Parekh  2 , Sundar Jagannath  2 , Shambavi Richard  2 , Ruben Niesvizky  1 , Mark Bustoros  1
Affiliations
Multicenter Study

Absolute lymphocyte count after BCMA CAR-T therapy is a predictor of response and outcomes in relapsed multiple myeloma

Mateo Mejia Saldarriaga et al. Blood Adv. .

Abstract

B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T cells (CAR-Ts) used in multiple myeloma (MM) are rapidly becoming a mainstay in the treatment of relapsed/refractory (R/R) disease, and CAR-T expansion after infusion has been shown to inform depth and duration of response (DoR), but measuring this process remains investigational. This multicenter study describes the kinetics and prognostic impact of absolute lymphocyte count (ALC) in the first 15 days after CAR-T infusion in 156 patients with relapsed MM treated with the BCMA-targeting agents ciltacabtagene autoleucel and idecabtagene vicleucel. Patients with higher maximum ALC (ALCmax) had better depth of response, progression-free survival (PFS), and DoR. Patients with ALCmax >1.0 × 103/μL had a superior PFS (30.5 months vs 6 months; P < .001) compared with those with ≤1.0 × 103/μL, whereas patients with ALCmax ≤0.5 × 103/μL represent a high-risk group with early disease progression and short PFS (hazard ratio, 3.4; 95% confidence interval, 2-5.8; P < .001). In multivariate analysis, ALCmax >1.0 × 103/μL and nonparaskeletal extramedullary disease were the only independent predictors of PFS and DoR after accounting for international staging systemic staging, age, CAR-T product, high-risk cytogenetics, and the number of previous lines. Moreover, our flow cytometry data suggest that ALC is a surrogate for BCMA CAR-T expansion and can be used as an accessible prognostic marker. We report, to our knowledge, for the first time the association of ALC after BCMA CAR-T infusion with clinical outcomes and its utility in predicting response in patients with R/R MM.

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Conflict of interest statement

Conflict-of-interest disclosure: J.M. reports receiving advisory or consulting fees from Janssen. C.R. reports receiving research funding from Janssen. D.P. reports receiving consulting fees from Sanofi. M.M. reports receiving advisory or consulting fees from bluebird bio, CRISPER/Vertex, and Incyte. S.L. reports receiving advisory or consulting fees from Adaptive Biotechnologies, Alexion Pharmaceuticals, Bristol Myers Squibb, Janssen, Karyopharm Therapeutics, Takeda, Pfizer, Oncopeptides, and Caelum Biosciences, and patents and royalties effective 1 January 2041; research funding from Celgene and Sanofi; and honoraria from Clinical Care Options and Regeneron. R.R. reports receiving advisory or consulting fees from TScan Therapeutics. S.Y. reports receiving advisory and consultancy fees from Kite Pharma and Bristol Myers Squibb. A.R. reports receiving advisory or consulting fees from Sanofi, Bristol Myers Squibb, and Adaptive Biotechnologies. S.P. reports receiving research funding from Amgen, Karyopharm, and Bristol Myers Squibb. S.J. reports receiving advisory or consulting fees from Bristol Myers Squibb, Janssen, Merck, Sanofi, Takeda, and Karyopharm. R.N. received honoraria and advisory fees from Bristol Myers Squib, Janssen, and Karyopharm, and received research funding from Celgene Inc, Takeda Inc, and Onyx Inc. S.R. reports receiving advisory or consulting fees from Bristol Myers Squibb and Janssen; and research support from Janssen, Bristol Myers Squibb, Gracell Biotechnologies, and C4 Therapeutics. M.B. reports receiving honoraria from Bristol Myers Squibb, Janssen, and Karyopharm; and consultancy fees from Bristol Myers Squibb, Janssen, Ipsen, and Menarini Silicon Biosystems. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Survival analysis according to ALC and other disease features. PFS by ALCmax (A), presence of high-risk cytogenetics (any of deletion 17p, t(4;14), t(14;16) or gain 1q) (B), and presence of nonparaskeletal EMD (non-PS EMD) (C) subgroups in the BCMA CAR-T cohort. PFS in patients treated with cilta-cel (D) and ide-cel (E).
Figure 2.
Figure 2.
Comparison of ALC kinetics according to clinical outcomes. ALC by depth of response status (A) and progression status (B) from days –5 through +15. Shaded area represents 95% CI.
Figure 3.
Figure 3.
ALC dynamics in BCMA and CD19 CAR-T–treated patients during days 0 through +15.
See this image and copyright information in PMC

References

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