Cellular and T cell engager Immunotherapy

Category: Cellular and T cell engager Immunotherapy

Splenomegaly is associated with high-tumor burden, prolonged cytopenia and adverse outcome after BCMA-directed CAR T-Cell therapy

(PA-104) Splenomegaly Is Associated with High-tumor Burden, Prolonged Cytopenia and Adverse Outcome After BCMA-directed CAR T-cell Therapy

Thursday, September 18, 2025

TW

Thomas c. Wiemers

resident
Department of Hematology, Hemostaseology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany

Introduction: Chimeric antigen receptor (CAR) T-cell therapies targeting B-cell maturation antigen (BCMA) have emerged as a transformative treatment modality for patients with relapsed or refractory multiple myeloma (RRMM). Despite impressive initial responses, the majority of patients ultimately relapse, and treatment is frequently complicated by substantial toxicities, particularly hematologic adverse events. Splenic enlargement has previously been associated with disease burden in RRMM. In this study, we investigated the prognostic significance of spleen volume in the context of BCMA-directed CAR T-cell therapy.

Methods: We retrospectively analyzed clinical and imaging data from 73 patients with RRMM who received either idecabtagene vicleucel or ciltacabtagene autoleucel at the University Hospital Leipzig. Spleen volume was assessed using CT–based volumetric analysis performed prior to lymphodepletion and 30 days post-CAR T-cell infusion. Spleen size measurements were correlated with established surrogates of tumor burden, including metabolic tumor volume (mTV) derived from PET/CT and serum levels of soluble BCMA (sBCMA). Additionally, we evaluated the association between spleen volume and prolonged hematologic toxicity, progression-free survival (PFS), and overall survival (OS).

Results:

Baseline clinical and demographic characteristics were similar between patients with and without splenomegaly, which was defined using a volumetric cutoff of >340 cm³. Spleen volume was associated with post-treatment hematologic toxicity. Specifically, patients who developed severe thrombocytopenia following CAR T-cell infusion had significantly larger spleen volumes than those without (304.9 vs. 207.9 cm³; p < 0.01). Likewise, patients experiencing prolonged thrombocytopenia exhibited greater spleen volumes compared to those with more transient cytopenias (302.0 vs. 206.8 cm³; p < 0.01). Assessment of tumor burden revealed elevated mTV on PET/CT imaging (602.0 vs. 86.9 mL; p < 0.05), as well as higher circulating levels of sBCMA (54.0 vs. 4.5 ng/mL; p < 0.05), indicating an association between spleen size and systemic disease burden.

Furthermore, splenomegaly was significantly associated with inferior PFS (HR: 8.9, 95% CI: 2.29–35.1; p < 0.01) and OS (HR: 8.3, 95% CI: 1.4–49.7; p < 0.05), outperforming established prognostic indicators such as sBCMA levels, the EASIX score, and the CAR-Hematotox score.

Conclusions: Spleen volume represents a robust and easily measurable prognostic biomarker in patients undergoing BCMA-directed CAR T-cell therapy. These findings underscore the potential utility of incorporating spleen size into routine clinical assessment protocols. Moreover, they highlight the rationale for exploring therapeutic strategies aimed at reducing splenic volume as a means to mitigate toxicity and improve patient outcomes