Pre-treatment Pulmonary Function Testing Has Limited Utility In B-cell Lymphoma Treated with CD19 CAR T-cells

Pulmonary function tests (PFT) are recommended for hematopoietic cell transplantation (HCT) evaluation. However, their prognostic value in chimeric antigen receptor T-cell (CAR-T) therapy remains unclear. We assessed the predictive significance of PFTs and pulmonary comorbidity classifications, per the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), in B-cell lymphoma patients undergoing autologous CD19-CAR-T therapy. Single-center retrospective analysis encompassing 192 patients with relapsed/refractory (R/R) B-cell lymphoma, treated with commercial and point-of-care CD19-directed CAR-T therapy. Pre-therapy PFT were conducted, and patients were stratified into 3 HCT-CI-based pulmonary comorbidity grades, utilizing forced expiratory volume in 1 second (FEV1) and single-breath diffusing capacity for carbon monoxide (DLCO). Outcomes and toxicities were evaluated using univariate and multivariable Cox regression, logistic regression, Kaplan-Meier method, and spline models. Pulmonary comorbidity measures were not correlated with overall response rates or immune-toxicities, including cytokine release syndrome grade>2 and immune effector cell-associated neurotoxicity grade>2. Categorical FEV1, DLCO, and pulmonary comorbidity level did not correlate with overall survival (p=0.3, p=0.4, p=0.6, respectively) or progression free survival (PFS) (p=0.058, p>0.9, p=0.2, respectively). FEV1 as continuous measure was associated with reduced PFS in a multivariable model (HR 0.87 [95% CI 0.78-0.96], p=0.007). Spline modeling demonstrated a linear correlation between FEV1 and PFS. Categorical FEV1, DLCO, and pulmonary comorbidity level failed to predict therapy efficacy or toxicity. FEV1 as continuous measure was the sole PFT measure associated with PFS, independent of OS or severe toxicities.