Immunotherapy and associated immune-related adverse events at a large UK centre: a mixed methods study.

Background: The development and rapid uptake of immune checkpoint inhibitors (CPI) has changed the outlook for patients with cancer. However, CPIs have different adverse event (AE) profiles to other systemic therapies, and prompt AE management is essential to assure optimal outcomes. In order to understand what and when adverse events are experienced, reported and managed during CPI treatment, a mixed methods study was conducted, including a case note review of patients who were receiving immunotherapy and semi-structured interviews with patients to understand their experience, management and reporting of AEs after receiving immune CPI treatment.

Methods: This mixed methods study was conducted at a large cancer hospital in the United Kingdom. A case note review identified how and where patients reported AEs. Data relating to patients with lung, bladder, prostate and head & neck cancers who received CPI treatment between 01/04/2015 and 31/07/2018 were extracted from e-prescribing databases and clinical data were included for analysis at a single time point (31 July 2018). Semi-structured interviews were conducted with patients receiving CPI treatment, exploring experience of AEs and reasons for delays in AE reporting and management.

Results: Sixty-two patients were included in the case note review, with 78 AEs being experienced by 36 patients (58%), including one patient experiencing 10 AEs. Serious AEs were experienced by 12 patients (19%) and ten AEs (17%) required oral steroids as treatment. The majority of AEs were reported to clinicians prior to further dosing, although milder AEs were often not addressed until subsequent clinic appointments. Interviews with 13 patients yielded major themes: variability, causality, decision making and impact.

Conclusion: Most CPI-associated AEs are manageable if reported and treated promptly. Both the case note review and interviews found that reporting of non-serious AEs is often left until routine clinic visits, despite impacting patient experience, leaving the opportunity for AEs to be left unreported and implying a potential benefit for real time monitoring. Our study highlights a need to provide patients with reminders around AEs and their timely reporting even when apparently innocuous; patients must understand that AEs can occur at any cycle and even following treatment completion.