Rechallenging with immune checkpoint inhibition after a treatment-limiting immune-related adverse event.

Abstract

3053 Background: Immune checkpoint inhibition (ICI) with cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), or programmed death ligand-1 (PD-L1) blockade can be associated with the development of immune related adverse events (irAE), many of which can be treatment-limiting. Due to an absence of randomized controlled trials, the current approach in regards to ICI discontinuation versus rechallenging remains controversial. Methods: We assessed all patients who had received ICI at a single academic institution from 5/2015 to 1/2019, identifying those who had delays in their treatment. Retrospective chart review was performed to determine type of ICI, type and grade of irAE, treatment of irAE, and recurrence and grades of irAE if ICI was resumed, as well as to assess overall survival (OS). Results: 562 patients received ICI (lung cancer [232, 41%], melanoma [66, 12%], kidney cancer [43, 8%], bladder cancer [27, 5%], and other cancers [194, 34.5%]) from 5/2015 – 1/2019. Of these, 121 (22%) had a treatment-limiting irAE (most commonly dermatitis [24%], colitis [17%], pneumonitis [14%], and hepatitis [12%]). Of the patients who had ICI held, 80/121 (66%) were eventually rechallenged, while 41/121 (34%) discontinued permanently. When rechallenged with ICI, 47/80 (59%) had no further treatment-limiting irAEs, 16/80 (20%) had a recurrence of the same irAE, and 17/80 (21%) developed a different irAE. Of those who were rechallenged, only 17/80 (21%) ultimately had to discontinue because of a second irAE. At a median follow up time of 12.1 months, median OS was not reached in those patients who experienced a treatment limiting irAE and was 8.1 months in those who did not (hazard ratio [HR] for death, 0.33; 95% CI 0.23 – 0.48; p < 0.001). At 12 months from initiation of ICI, 77.0% of patients who had a treatment-limiting irAE were alive, compared to 39.6% of those who did not have an event. Restarting ICI after a treatment-limiting irAE was not associated with a change in OS (HR 0.66 [95% CI 0.27 – 1.66], p = 0.38). Conclusions: Patients who discontinued ICI secondary to irAEs had relatively low rates of recurrent toxicity when rechallenged with treatment. These patients were just as likely to develop a new toxicity as a recurrence of the original irAE, and relatively few had to discontinue permanently. Development of a treatment-limiting irAE was associated with improved OS compared to those who did not. This study suggests that rechallenging with ICI may be safe in selected patients, though this did not have an impact on OS.