Developing alert thresholds and self-management advice for people receiving immune checkpoint inhibitors: a...

Remote monitoring using electronic patient-reported outcomes (ePROs) may help identify immune-related adverse events (irAEs) and direct self-management. There is no consensus regarding thresholds to alert providers about potentially severe irAEs or when to instigate evidence-based self-management. We aimed to develop consensus around alert thresholds and self-management advice for side-effects suggestive of an irAE which can be deployed as part of remote monitoring systems.

A two-round international modified Delphi survey including co-authors of major international irAE guidelines and selected immuno-oncology experts was conducted. Round 1 (R1): participants reviewed alert thresholds graded as per the Common Terminology Criteria for Adverse Events (CTCAE) and self-management statements for 36 side-effects. Participants stated whether they agreed or disagreed with the proposed thresholds and self-management statements. If ≥ 75% of participants agreed, consensus was reached. Prior to Round 2 (R2), thresholds and self-management statements that did not reach consensus in R1 were modified. In R2, participants were asked whether they agreed or disagreed with the modifications.

In R1, 34 participants responded (North America: 18, 52.9%; Europe: 12, 35.3%; Asia-Pacific: 4, 11.8%; median duration of experience in current role, 13.5 years (range, 3-46 years)), with 33 complete responses received. Twenty-nine alert thresholds and 33 self-management statements reached consensus. For R2, seven alert thresholds were increased from CTCAE Grade 1 to 2 based on participant comments, and three self-management statements were amended. Six self-management statements which achieved consensus were amended and re-presented in R2. In R2, 31 participants responded (North America: 18, 58.1%; Europe: 9, 29%; Asia-Pacific: 4, 12.9%; median duration of experience in current role, 13 years (range, 3-40 years)), with 30 complete responses received. All seven alert thresholds and nine self-management statements achieved consensus.

This survey developed international consensus regarding alert thresholds and self-management advice for common, clinically relevant side-effects suggestive of an irAE for ePRO monitoring systems with international applicability. Self-management statements will inform written materials for patients.