The efficacy and safety of ruxolitinib as an add-on therapy to corticosteroids for patients with severe checkpoint inhibitor pneumonitis.

e24121 Background: Although immune checkpoint inhibitors (ICIs) have improved survival of patients with malignancies, they also bring forth the immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) stands out as a prominent complication following ICI therapy, while a substantial proportion of CIP cases present with severe manifestations, often leading to life-threatening outcomes. The management of severe and refractory CIP is challenging. This study was aimed to evaluate the efficacy and safety of ruxolitinib as an add-on therapy to corticosteroids for patients with severe CIP. Methods: In this investigator-initiated, multicenter, randomized, open-label, phase 2 trial, cancer patients with CTCAE grade (G) 3 or G4 CIP after ICIs therapy were enrolled. CIP patients were randomly assigned in a 1:1 ratio (randomized block method) to corticosteroids administration (the initial dosage was more than prednisone 1mg/kg/d or equivalent) or corticosteroids with add-on ruxolitinib administration (5mg twice a day for 2 weeks, followed by 5mg once a day for 2 weeks). The primary end point was the proportion of patients with a prednisone daily dosage of no more than 10mg and improvement to G1 CIP at week 8. Results: From April 2023 to Jan 2024, 19 patients were enrolled. There were 17 cases of G3 CIP and two cases of G4 CIP. Eleven cases were assigned to corticosteroids group (C group), and 8 cases were assigned to corticosteroids with add-on ruxolitinib administration group (R group). Fourteen patients completed 8 weeks of follow-up. Five cases (5/6, 83.3%) in the R group and three cases (3/8, 37.5%) in the C group improved to G1 CIP and received ≤prednisone 10mg daily at week 8. One patient in the R group and three cases in the C group failed to taper to 10mg/d prednisone or had G2-3 CIP. Two patients in the C group died from CIP. Two cases in R group and three cases in C group were still under follow-up. The G3 or higher treatment-related AEs (TRAEs) occurred in three patients, including one case of aspiration pneumonia in C group and two cases of COVID-19 (one in each group). Conclusions: Corticosteroids with add-on ruxolitinib administration could improve clinical responsiveness for severe CIP patients. The safety profile was controllable and favorable. Ruxolitinib could provide a valuable promising therapeutic option for cancer patients with severe CIP. Clinical trial information: NCT05899725 .