# Outcomes and Adverse Events in Patients with Cancer after Diagnosis of Immunotherapy-Associated Diabetes Mellitus: A Retrospective Cohort Study

## TL;DR

This study examines the outcomes of cancer patients who experience diabetes from immunotherapy and whether resuming treatment affects future adverse events or cancer progression.

## Contribution

The study provides first insights into the risks and benefits of resuming immunotherapy after diabetes mellitus as an adverse event.

## Key findings

- No significant difference in cancer progression or death was found between patients who resumed or discontinued immunotherapy after CPI-DM.
- Patients who resumed CPIs had a higher, though not statistically significant, rate of subsequent immune-related adverse events.
- The study highlights the need for a nuanced decision-making approach when considering resuming CPIs after CPI-DM.

## Abstract

Checkpoint-inhibitor-associated diabetes mellitus is a severely morbid immune-related adverse event that occurs from immunotherapy treatment during cancer therapy. Many patients and clinicians opt to discontinue therapy after this adverse event occurs while others choose to resume treatment. There are currently no data to inform this decision in terms of risks and benefits to the patient. This study aims to determine future risk for immune-related adverse events and cancer outcomes in patients who make this decision after experiencing diabetes mellitus.

Immune checkpoint inhibitor (CPI)-induced diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE). Patients and providers fear that continuing CPIs puts patients at risk for additional irAEs and thus may discontinue therapy. Currently, there are little data to inform this decision. Therefore, this study aims to elucidate whether discontinuing CPIs after diagnosis of CPI-DM impacts the development of future irAEs and cancer outcomes such as progression and death. Patients who developed CPI-DM during cancer treatment at UCSF from 1 July 2015 to 5 July 2023 were analyzed for cancer outcomes and irAE development. Fisher’s exact tests, Student t-tests, Kaplan–Meier methods, and Cox regression were used as appropriate. Of the 43 patients with CPI-DM, 20 (47%) resumed CPIs within 90 days of the irAE, 4 (9%) patients restarted after 90 days, and 19 (44%) patients never restarted. Subsequent irAEs were diagnosed in 9 of 24 (38%) who resumed CPIs and 3 of 19 (16%) who discontinued CPIs (p = 0.17). There was no significant difference in death (p = 0.74) or cancer progression (p = 0.55) between these two groups. While our single-institution study did not show worse cancer outcomes after discontinuing CPIs, many variables can impact outcomes, which our study was not adequately powered to evaluate. A nuanced approach is needed to decide whether to continue CPI treatment after a severe irAE like CPI-DM.