CHIMERIC antigen receptor T (CAR-T) cell immunotherapy, specifically targeting the B-cell maturation antigen (BCMA) has been a breakthrough step in the treatment of relapsed or refractory (R/R) multiple myeloma (MM). Previous studies have shown that CAR-T cell expansion post-infusion informs depth and duration of response (DoR), however, protocols for measuring this process have not been fine-tuned.
A multicentre study led by Mateo Mejia Saldarriaga, Meyer Cancer Center, New York, USA aimed to assess the levels of overt lymphocytosis in the peripheral blood after CAR-T infusion in RRMM. The focus was on the kinetics of absolute lymphocyte count (ALC) within the first 15 days following CAR-T infusion to assess the relationship of these levels to immune-mediated toxicities and its prognostic significance.
The cohort comprised patients with R/R MM who received BCMA-CAR-T immunotherapy between 2017 and 2023 across the three institutions. Baseline ALCs were taken 5 days before treatment and for 15 days once therapy has commenced. Results showed that patients with higher maximum ALC (ALCmax) demonstrated superior progression-free survival and DoR. Notably, patients with ALCmax ≤0.5×103/μL were identified as high-risk, experiencing early disease progression and significantly shorter PFS.
This study marks the first detailed analysis of the relationship between ALC and clinical outcomes in R/R MM patients treated with BCMA CAR-Ts. It highlights the prognostic utility of monitoring ALC post-infusion, offering a practical method for early prediction of patient outcomes, and potentially guiding treatment adjustments. Future research could further elucidate the immune mechanisms behind these observations and explore how these insights could be extrapolated to enhance CAR-T therapy efficacy.
Katie Wright, EMJ
Reference
Mejia Saldarriaga M et al. Absolute lymphocyte count after BCMA CAR-T therapy is a predictor of response and outcomes in relapsed multiple myeloma. Blood Adv. 2024;8(15):3859-3869.
