Role of Pulmonary Function Tests to Predict Complications After Chimeric Antigen Receptor T-Cell Therapy.

Abstract

Background: Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of certain hematologic malignancies, but toxicities limit efficacy. The role of pre-CAR-T pulmonary function testing (PFT) to predict toxicities is unclear.

Objective: Our aim was to examine the association between PFTs obtained prior to CAR-T and subsequent complications in patients with lymphoma.

Study design: We conducted a retrospective study of patients who underwent standard-of-care CAR-T at our institution with pretherapy PFTs. Race-neutral normative equations from the Global Lung Initiative were used to generate percent-predicted values (PPV) for spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO). Lung function score (LFS) was calculated by combining the forced expiratory volume in the first second (FEV₁) and the diffusion capacity of the lung for carbon monoxide corrected for hemoglobin level (cDLCO) in an equally distributed manner, with higher score denoting worse lung function. Binary logistic regression models were used to compare the association of PFTs with complications after CAR-T. Cox regression models were additionally fit to identify predictors of mortality.

Results: Of 218 individuals who underwent CAR-T therapy, 66 had PFTs performed within 12 months prior to lymphodepletion. Higher LFS was associated with higher risk of CRS (OR 4.3, 95% CI, 1.4-29, P = .048), after adjusting for lines of treatment. When adjusting for lines of treatment, both FEV₁ (OR = 0.96, 95% CI, 0.93-0.99, P = .05) and FVC (OR = 0.96, 95% CI 0.92-0.99, P = .03) are protective for ICANS. PFT abnormalities were not associated with early or late mortality.

Conclusion: The combination of pre-CAR-T spirometry and cDLCO may help clinicians understand the risk for toxicities after CAR-T cell therapy.