(PA-193) Absolute Lymphocyte Count (ALC) ≥1,000 Is as a Surrogate of Car‑T Cell Expansion and a Readily Available Biomarker to Predict Outcomes in Relapsed/refractory Multiple Myeloma (RRMM)

Following the approval of anti-BCMA CAR-T cells as living drugs, there is an urgent need to identify biomarkers that enable tailored strategies to improve post-infusion outcomes. While measuring CAR‑T cell expansion is informative, it remains technically challenging in most centers. We aim to evaluate whether the absolute lymphocyte count (ALC) during the first 14 days after CAR-T infusion could serve as a practical surrogate for CAR-T cell expansion and predict clinical outcomes.

Methods:

We retrospectively analyzed 65 relapsed/refractory multiple myeloma patients treated with anti-BCMA CAR‑T cells at our center between April 2018 and November 2024. ALC was recorded at baseline and daily for the first 14 days post‑infusion. Patients were stratified into those reaching at any time point a maximum ALC ≥ 1,000 cells/mm³ vs those who did not.

Results:

Patients had received a median of 3 prior lines of therapy (range, 1–10) before CAR-T treatment. The overall median progression-free survival (PFS) was 11.3 months (95% CI, 6.8–12.9). Of the 65 patients, 37 (56.9%) achieved ALCmax ≥ 1,000 cells/mm³, while 28 (43.1%) did not.

Baseline characteristics were largely similar between groups, except that the ALCmax < 1,000 cohort had received more prior therapies ( > 3 lines: 54% vs. 27%; P = .03) and exhibited a higher rate of extramedullary disease (EMD: 18% vs. 3%; P = .048). No significant differences were observed in terms of cytogenetic risk, ISS stage, triple-class refractoriness, bone marrow plasma cell infiltration (BMPC) > 50%, marrow B- or T-cell populations, or the CD27−/CD27+ T-cell ratio.

At one month post‑infusion, 59% of patients in the ALCmax < 1,000 group achieved MRD negativity vs 94% in the ALCmax ≥ 1,000 group (P = .001). No significant differences were found for the occurrence of CRS (86% vs 97%; P = .083) or ICANS (18% vs 16%; P = .86), neither in terms of frequency or severity of the episodes.

Patients with ALCmax < 1,000 had markedly inferior outcomes: median PFS of 6.8 months (95% CI, 2.5–11.2) versus 17.5 months (95% CI, 11.4–23.6); HR 3.4 (95% CI, 1.9–6.1) (P < .001) and median overall survival (OS) of 11.7 months (95% CI, 7.8–15.7) versus not reached; HR 3.1 (95% CI, 1.6–6.2) (P = .001).

In multivariate Cox regression adjusting for high-risk cytogenetics, EMD at screening, BMPC > 50%, triple-class refractoriness, and ISS stage III, ALCmax < 1,000 remained an independent predictor of poorer outcomes. The HR for PFS was 2.4 (95%CI 1.8–5.1; P = .017), and for OS was 3.1 (95%CI 1.2–7.6; P = .017).

Conclusions:

Early post-infusion ALC serves as a reliable surrogate for CAR-T cell expansion, stratifying patients into two groups with significantly different survival outcomes despite comparable baseline profiles. Patients failing to achieve ALCmax ≥ 1,000 cells/mm³ may warrant early, tailored interventions to mitigate progression risk associated with suboptimal CAR-T expansion.