Rechallenge with immune checkpoint inhibitors beyond severe toxicities, an utopia?

Abstract

e14601 Background: Immunotherapy (IO) has substantially improved clinical outcomes in different types of tumours. Its use has been associated with so-called immune-related adverse effects (IrAEs), some of them, potentially severe and/or fatal. Current guidelines recommend discontinuation of IO in severe IrAEs (grades 3/4). Therefore, there is very limited evidence about the safety of “rechallenge” or re-treatment with IO in patients who have experienced severe toxicities. The objective of this study is to describe the toxicities experienced by patients treated with IOs in our unit and identify the recurrence rate of these rEAIs in those patients in whom immunotherapy is re-administered. Methods: We carried out a retrospective analysis of patients treated with IO from January 2015 to April 2021. As inclusion criteria, we selected the condition that the patients have had at least one tumour reevaluation after the IO was started. We have collected clinical and epidemiological variables, efficacy (mesured by RECIST 1.1 and iRECIST criteria) and, as well as recorded toxicity data (mesured by CTCAE V4.3). Results: 220 patients have received some IO drug between the indicated periods. The characteristics of the patients are shown in the attached table. 66% of patients treated with IO have received anti-PD-1/PD-L1 therapy as monotherapy. 60% (134/220) of patients experienced at least 1 IrAE. Of the IrAEs, only 20% were grade 3/4. Only 34 (25%) of the 134 patients who experienced any toxicity required IO stop. Of these 34, only 17 patients achieved retreatment with IO after resolution of initial toxicity. In 14 of the 17 patients who underwent rechallenge, IO was permanently discontinued due to recurrence of the same IrAEs. The IrAE that recurs most frequently after rechallenge was colitis (35% of cases), followed by nephritis (28%). 41% of the patients who experienced toxicity had an objective response to their disease, compared to only 9% in those who did not present any IrAE, which was statistically significant (p<0.05%). Conclusions: In our serie, rechallange with IO after toxicity was associated with the appearance of the same IrAE, which is consistent with what has been published in other series. We are doing further analyses in order to explore IO toxicity deeply, increasing the number of patients which have received immune checkpoint inhibitors.[Table: see text]