Abstract
Pulmonary function tests (PFTs) 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 patients with B-cell lymphoma undergoing autologous CD19 CAR-T therapy. Single-center retrospective analysis encompassing 192 patients with relapsed/refractory B-cell lymphoma (BCL), treated with commercial and point-of-care CD19-directed CAR-T therapy. Pretherapy PFTs were conducted, and patients were stratified into 3 HCT-CI-based pulmonary comorbidity grades, using 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 (OS; P = .3, P = .4, P = .6, respectively) or progression-free survival (PFS; P = .058, P > .9, P = .2, respectively). FEV1 as a continuous measure was associated with reduced PFS in a multivariable model (hazard ratio, 0.87; 95% confidence interval, 0.78-0.96; P = .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 a continuous measure was the sole PFT measure associated with PFS, independent of OS or severe toxicities.