Pralsetinib-associated pneumonia in RET fusion-positive non-small cell lung cancer.

Objective: Oncogenic alternation in RET is one of the important targets of non-small cell lung cancer (NSCLC). Pralsetinib has shown great efficacy in RET fusion-positive NSCLC, but a series of adverse reactions will inevitably occur in the meantime. We aimed to explore the clinical characteristics of patients with pneumonia and recognition it in early stage, so patients could longer benefit from pralsetinib.

Methods: This is a multicenter, retrospective study. RET fusion-positive advanced NSCLC patients who developed pneumonia during pralsetinib treatment from January 2020 to December 2022 were included. Clinical data, time to onset of pneumonia, methods of pneumonia diagnosis, treatment with pneumonia, prognosis of pneumonia, and the effect of pneumonia on the efficacy of pralsetinib.

Results: A total of 8 patients with pneumonia were included in the study, most of which were non-smoking female patients and the main fusion gene was KIF5B (87.5%), which was consistent with the general characteristics of RET fusion population. The median occurrence time of pralsetinib-associated pneumonia was 2.15 (range 1.1-6.63) months. All patients were infected by opportunistic pathogens, and the most common pathogen was human herpesviruses and pneumospora yerbii. Fever was always the first symptom, and timely anti-infective treatment including antibiotics, antiviral drugs, and antifungal drugs was effective. Until February 28, 2023, the median follow-up time was 18.7 months, the mean PFS of patients was 17.4 months, and the median PFS was not reached. Fortunately, patients who restarted pralsetinib after infection control continued to benefit.

Conclusions: Opportunistic infection may be a unique adverse effect of pralsetinib. During the treatment of pralsetinib, we should be vigilant about the occurrence of pneumonia and achieve early recognition and timely treatment.