Immune checkpoint inhibitor (ICI) rechallenge after immune-related adverse events (irAE) requiring hospitalization: A single-center 10-year experience.

person Chia-Yun Wu Far Eastern Memorial Hospital, New Taipei City, Taiwan info_outline Chia-Yun Wu, Leyre Zubiri, Sherin Juliet Rouhani, Ross D. Merkin, Allison Holt, Ayo Samuel Falade, Kelley Grealish, Nora Hathaway, Kerry Lynn Reynolds

Authors person Chia-Yun Wu Far Eastern Memorial Hospital, New Taipei City, Taiwan info_outline Chia-Yun Wu, Leyre Zubiri, Sherin Juliet Rouhani, Ross D. Merkin, Allison Holt, Ayo Samuel Falade, Kelley Grealish, Nora Hathaway, Kerry Lynn Reynolds Organizations Far Eastern Memorial Hospital, New Taipei City, Taiwan, Massachusetts General Hospital, Boston, MA, Massachusetts General Hospital Cancer Center, Boston, MA, Massachusetts General Hospital, Harvard Medical School, Boston, MA, University of Massachusetts Chan Medical School, Worcester, MA, Massachusetts General Brigham Salem Hospital, Salem, MA, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA Abstract Disclosures Research Funding Pugh Scholar Award The Oversea Training Scholarship of Far Eastern Medical Foundation Background: ICI rechallenge after irAE has become a significant clinical dilemma, with irAE recurrence rates of 30-40% after rechallenge. Here we examine factors influencing ICI rechallenge rates across a 10-year period at the Massachusetts General Hospital (MGH), where the Severe Immunotherapy Complications service is available to provide multidisciplinary irAE expertise. Methods: We included patients admitted to MGH for an irAE from August 2011 to July 2023. We collected baseline demographics, ICI regimens, and irAE features. The choice of ICI used at rechallenge was grouped into 3 categories: 1) restarting an ICI within the same class, 2) switching classes (CTLA-4 to PD-(L)1 or vice versa), or 3) de-escalating from combination to monotherapy. Chi-square and Mann-Whitney U tests were applied to descriptive statistics. Results: Among 5882 patients treated with ICI, 671 (11.4%) patients were admitted for irAE. The median age was 67.6 (IQR, 59-74.9) years and 58% were male. Initial ICI regimens consisted of anti-PD-(L)1 (64.8%), anti-CTLA4 (10.9%), and ICI combinations (24.3%). 174 of 671 patients (25.9%) were rechallenged after an irAE requiring hospitalization. Rechallenge was common after rheumatologic, endocrine, dermatologic irAE and GI irAE, but rare after cardiac, neurologic, or pulmonary irAE (Table 1). The median time to rechallenge was 25 days (IQR 18-91) after endocrine irAE and 72 days (IQR 40-209) after non-endocrine irAE (p<0.001). Rechallenge was more common in melanoma (35%, p<0.001), and less common in lung (13.6%, p<0.001) and GU cancers (10%, p=0.003). Rechallenge rates were significantly higher in patients initially on combination therapy (39.6%) versus PD-(L)1 monotherapy (15.5%), p<0.001. Of those rechallenged, 43.2% initially on combination therapy were de-escalated to monotherapy and 53% were restarted within the same class. Amongst the PD-(L)1 monotherapy group, 88.4% were restarted within the same class and 11.6% switched classes. Conclusions: Here we examine practice patterns at a large academic center, where 25.9% of patients with irAE requiring hospitalization were rechallenged. Rechallenge was more prevalent in patients with melanoma or on ICI combination therapy, whereas it was less frequent following cardiac, neurologic, or pulmonary irAE. Under adequate risk-benefit evaluation, close monitoring, and multidisciplinary care, ICI rechallenge can be considered. Frequency of Hospitalized irAEs (%) Number Rechallenged (%) Median Days to Rechallenge (IQR) GI (n=243) 24.7 33.7 76 (49-157) Endocrine (n=144) 14.6 42.4 25 (18-91) Pulmonary (n=144) 14.6 11.8 111 (35-438) Hepatic (n=135) 13.7 21.5 121 (38-205) Neurology (n=95) 9.7 9.5 664 (157-714) Cardiac (n=74) 7.5 2.7 111 Dermatology (n=57) 5.8 35.1 41 (17-77) Rheumatology (n=31) 3.2 48.4 56 (29-340) Others (n=61) 6.2 22.0 81 (49-205)