Severe delayed pulmonary toxicity following PD-L1-specific CAR-T cell therapy for non-small cell lung cancer

Objectives: This phase I study aimed to evaluate the antitumor effect and safety of programmed death-ligand-1 (PD-L1)-targeting autologous chimeric antigen receptor T (CAR-T) cells for patients with non-small cell lung cancer (NSCLC).

Methods: Programmed death-ligand-1-specific CAR-T cells were generated using lentiviral transduction. Four patients with NSCLC were recruited, but only one patient was finally involved. CAR-T cells were infused on three different days (total dose during therapy, 1 × 10⁶ CAR-T cells kg^-1 body weight). The date on which the patient received the first CAR-T cell infusion was designated as Day 0.

Results: Circulating CAR-T cells accounted for 3.30% of the patient's peripheral blood T cells detected by FACS analysis during the first follow-up (Day +29). The chest CT scan showed subtle tumor shrinkage (stable disease). On Day +43, the patient developed pyrexia without any known causes and dyspnoea that rapidly deteriorated to respiratory failure in 3 days. The chest X-ray and CT scan showed bilateral extensive pulmonary infiltration in addition to the tumor silhouette on the left upper lung. The interleukin (IL)-6 levels in serum dramatically increased (> 100-fold). The patient was immediately transferred to the ICU where he received oxygen and intravenous infusions of tocilizumab and methylprednisolone. His symptoms rapidly improved and the pulmonary inflammation gradually resolved.

Conclusion: The clinical manifestations and test findings for this patient with NSCLC might represent unique clinical manifestations of solitary organ damage secondary to PD-L1-specific CAR-T cell therapy. The differential diagnosis, underlying mechanism and prevention and treatment strategies for such complications have also been discussed.