Baseline Spleen Volume is Independently Associated With Survival After CD19‐Directed Chimeric Antigen Receptor T‐Cell Therapy in Relapsed/Refractory Diffuse Large B‐Cell Lymphoma

Clinical outcomes after CD19‐directed chimeric antigen receptor (CAR) T‐cell therapy in patients with relapsed or refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) remain heterogeneous, underscoring the need for improved risk stratification. As CAR T‐cell efficacy is shaped not only by tumor‐intrinsic features, host‐related factors may also contribute to outcome variability. The spleen, the largest secondary lymphoid organ and a key regulator of immune cell trafficking, is a biologically plausible yet underexplored imaging marker in this setting. We retrospectively analyzed 88 patients with r/r DLBCL and available baseline imaging who received commercial CD19‐directed CAR T‐cell products between September 2019 and July 2025. Spleen volume was analyzed as a continuous variable (per 100 mL), without dichotomization or prespecified cutoffs, and clinical outcomes were examined in relation to baseline spleen volume. With a median follow‐up of 24.4 months, 2‐year progression‐free survival and overall survival were 40.9% and 56.4%, respectively. Higher baseline spleen volume was associated with inferior overall survival, a higher cumulative incidence of relapse/progression, and inferior post‐progression survival. The 24‐month risk of death increased progressively with increasing spleen volume. Baseline spleen volume remained independently associated with inferior overall survival after adjustment for established pretreatment risk factors (aHR 1.136 per 100 mL, 95% CI, 1.012–1.275; p = 0.030). Findings were consistent in sensitivity analyses including adjustment for BMI and after exclusion of patients with splenic lymphoma manifestations. Baseline spleen volume thus emerges as a readily available imaging‐derived marker that could complement established risk factors and refine baseline risk stratification prior to CAR T‐cell therapy in r/r DLBCL. Beyond the pretreatment setting, it also has potential utility for prognostication after relapse/progression.