Abstract 3619: Post CAR-T lymphocytosis as a surrogate of BCMA CAR-T expansion, response, and prognosis in multiple myeloma
Authors: Saldarriaga Mateo Mejia , Pan Darren , Unkenholz Caitlin , Mouhieddine Tarek , Fein Josh , Monge Jorge , Rosenbaum Cara , Pearse Roger , Jayabalan David , Gordillo Christian , Chan Hei Ton , Mapara Markus , Inghirami Giorgio , Lentzsch Suzanne , Reshef Ren , Rossi Adriana , Parekh Samir , Jagannath Sundar , Richards Shambavi , Niesvizky Ruben , Bustoros Mark 
Published: March 2024

Introduction: Expansion of chimeric receptor antibody (CAR)-T cells after infusion has been described as important marker in multiple myeloma (MM); however, the phenomenon of overt lymphocytosis has not been reported. We describe the kinetics of absolute lymphocyte count (ALC) after BCMA CAR-T in MM as a marker of depth of response and progression-free survival (PFS).

Methods: 158 patients (pts) were included (93 pts ciltacabtagene autoleucel (cilta-cel) and 65 pts idecabtagene vicleucel (ide-cel) from three institutions. Baseline characteristics, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), ALC on day -5 through 14, and outcomes were collected. A cohort of 84 pts who received CD19 CAR-T for non-Hodgkin lymphoma (NHL) as comparator. Peripheral blood (PB) flow cytometry was performed on days 7, 14 and 21 in 4 patients.

Results: Early ALC increase after BCMA CAR-T was frequent, with a median max ALC 1.3 × 103/uL (IQR 1-4.4) from a median baseline of 0. However, when compared to ide-cel, cilta-cel had a higher median Max ALC (2 × 103/uL (1 - 4.4) vs 0.8 (0.7 - 2.8), p &lt; 0.001), longer time-to-max ALC (11 vs 12 days, p = 0.003), and higher absolute ALC increase (2.1 × 103/uL vs 0.7 × 103/uL, p &lt;0.001), while there were no differences in ALC before lymphodepleting conditioning or day 0. Higher max ALC was associated with CRS (OR 4.8, CI 1.3-17.2, p 0.01). Max ALC and absolute increase in ALC were significantly associated with deeper response (VGPR vs PR or less), improved PFS and duration of response (DoR) in univariable analysis. Max ALC &gt;1 × 103/uL (HR 0.4, 0.2-0.7, p &lt;0.001) and non-paraskeletal EMD (HR 2.1, 1.2-.4, p &lt;0.01) remained associated with PFS/DoR in multivariable model after adjusting for CAR-T Product, high-risk cytogenetics, and number of previous lines. PB flow cytometry in 3 responder patients (max ALC range 2-14 × 103) showed expansion of CD3+ BCMA CAR-T from day 7 (BCMA CAR-T &lt;0.2% of CD3+ cells) to day 14 (BCMA CAR-T range 54-88.6%), while a non-responder (max ALC 0.4 × 103) patient had no expansion despite presence of CD3+ BCMA CAR-T at day 7, 14 and 21. BCMA CAR-T had higher max ALC when compared to CD19 CAR-T (median 1.3 × 103 vs 0.4 × 103 (0.2-0.7), p &lt; 0.001), while there were no differences in baseline ALC between BCMA and CD19 CAR-T. Median max ALC did not differ between response status after CD19 CAR-T (0.4 × 103 (0.2-0.7) vs 0.6 (0.3-0.7), p = 0.3).

Discussion: Post-CAR-T lymphocytosis is common after BCMA CAR-T therapy for MM and is associated with response, PFS, and DoR after adjusting for other prognostic variables. A cut-off of max ALC &gt; 1 × 103 identified patients with superior PFS, while max ALC &lt;0.5 × 103 represents high-rates of poor response and early progression. ALC expansion correlated with BCMA CAR-T expansion as assessed by flowcytometry, supporting ALC assessment as an accessible surrogate that is clinically applicable and accessible.

Citation Format: Mateo Mejia Saldarriaga, Darren Pan, Caitlin Unkenholz, Tarek Mouhieddine, Josh Fein, Jorge Monge, Cara Rosenbaum, Roger Pearse, David Jayabalan, Christian Gordillo, Hei Ton Chan, Markus Mapara, Giorgio Inghirami, Suzanne Lentzsch, Ren Reshef, Adriana Rossi, Samir Parekh, Sundar Jagannath, Shambavi Richards, Ruben Niesvizky, Mark Bustoros. Post CAR-T lymphocytosis as a surrogate of BCMA CAR-T expansion, response, and prognosis in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3619.