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

Abstract

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 eprescribing databases and clinical data were included for analysis at a single time point (31 July 2018). Semistructured 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.

Needs of Lung Cancer Patients Receiving Immunotherapy and Acceptance of Digital and Sensor-Based Scenarios for Monitoring Symptoms at Home—A Qualitative-Explorative Study

“…We reconstructed their needs regarding treatment and interaction with health care practitioners and proposed and discussed digital and sensor-based scenarios for the monitoring of common side effects of immunotherapy in lung cancer treatment. In line with previous qualitative research [ 19 , 22 ] immunotherapy in lung cancer meant a generally positive and promising outlook for our participants. At the same time, the reporting of potentially treatment-related symptoms to health care practitioners is not a trivial act: The participants in our sample had trouble to classify and differentiate between the symptoms they experienced.…”

“…Previous research has already pointed out the importance of real-time monitoring of symptoms and adverse events during immunotherapy in cancer patients [ 22 , 23 ]. In our study sample, the idea of digital and sensor-based monitoring turned out to be completely new to most of the participants and initially provoked rejection.…”

“…Jamieson and colleagues found the phenomenon of “personalization” of symptoms, meaning that patients would benchmark any symptom against what they think would be “usual” or “typical” for them as a person [ 22 ]. However, this aspect seems to be still under-researched.…”

“…The incidence of side effects under immunotherapies is, on average, higher when they were combined with chemotherapy [ 4 , 21 ], which is the case for the majority of lung cancer patients. Due to the fact that the specific side effects of immunotherapies, especially when administered as part of a combination therapy, are often difficult to assess by the patients themselves [ 19 ], real-time monitoring can contribute to a timely reporting of side effects [ 22 , 23 ]. Furthermore, such an approach could counteract the phenomenon of “selective reporting” [ 18 ] by health care practitioners and patients.…”

Assessment of hospitalization rates for immune-related adverse events with immune checkpoint inhibitors

“…A mixed methods study over a three-year period included 62 patients from a single center, most of which were treated for non-small cell lung cancer. 13 Nineteen percent of patients experienced a serious grade irAE and 58% had any grade irAE, most commonly gastrointestinal, fatigue, respiratory, and skin problems. Eight of the 62 patients reviewed required a hospital admission for irAE treatment.…”