Immune-related toxicity from immune checkpoint inhibitors linked to longer survival
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Key takeaways:
- Researchers observed better OS in patients with NSCLC who experienced immune-related adverse events.
- The analysis found similar age and sex distribution between those who did and did not experience such events.
Certain individuals with non-cell lung cancer who experienced immune-related adverse events due to immune checkpoint inhibitor therapy had improved survival outcomes, according to retrospective study data published in JAMA Network Open.
Individuals who experienced clinically meaningful immune-related adverse events that led to delays or discontinuation of immune checkpoint inhibitor therapy, or required treatment with steroids to revolve symptoms, had significantly longer median OS compared with who did not experience such events.
“To our knowledge, this study represents the largest contemporary clinical dataset evaluating the association between [immune-related adverse events] and survival in locally advanced or metastatic NSCLC, agnostic to [immune checkpoint inhibitor] agent,” researchers wrote.
“Developing a clinically meaningful [immune-related adverse event] was associated with longer OS in locally advanced or metastatic NSCLC,” they added. “Association with improved OS continued among patients requiring hospitalization for [immune-related adverse event] management.
Background, methods
Prior research has suggested an association between immune-related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) therapy and longer OS among patients with non-small cell lung cancer; however, such studies have been smaller in size with a poorly defined association between irAEs and OS.
Sarah Cook, MBBS, medical oncology resident at University of Calgary, and colleagues conducted an observational cohort study to examine the potential association between irAEs and their severity with OS in 803 patients with locally advanced or metastatic NSCLC while receiving ICIs.
The study included patients who received ICI therapy between March 1, 2014, and Nov. 30, 2021, with follow-up until March 31, 2023. Researchers completed data analysis April 26, 2023.
Cook and colleagues used the Alberta Immunotherapy Database to capture data from patients receiving ICIs in Alberta, Canada. The analysis included adults who received at least one cycle of ICI — either alone or with chemotherapy — agnostic to treatment line.
Establishing an association between irAEs and OS served as the study’s primary outcome. Researchers excluded patients with poor prognosis who may have died prior to developing irAEs from the OS analysis to mitigate immortal time bias.
Results, next steps
Patients with irAEs had a median age of 69.7 years (interquartile range, 63.1-75.2) and those without irAEs a median age of 67.5 years (interquartile range, 60.4-73.3).
Researchers observed a comparable sex distribution between the two groups, with 139 of 295 men (47.1%) and 156 of 295 women (52.9%) experiencing irAEs compared with 254 of 505 men (50.3%) and 251 of 505 women (49.7%) not experiencing irAEs.
After mitigating immortal time bias, the OS analysis included 611 patients, after which researchers determined an association between irAEs and OS (median OS with irAEs = 23.7 months, 95% CI, 19.3-29.1; median OS without irAEs = 9.8 months, 95% CI, 8.7-11.4).
Researchers did not report an OS difference between patients who received treatment in a hospital (median OS = 20.8; 95% CI, 11.7-30.6) compared with outpatient treatment (median OS = 25.6; 95% CI, 20.1-29.8).
Following Cox proportional hazards regression analysis using known prognostic characteristics, developing irAEs remained associated with OS in the total study cohort (HR = 0.53; 95% CI, 0.4-0.7).
Researchers also noted that the association did not appear to be compromised by hospitalization for severe toxic effects.
Despite the cohort size, additional studies are needed to better assess and understand specific parts of the treatment process for patients, according to researchers.
“The role of irAE severity in the survival of patients with NSCLC remains contentious,” researchers wrote. “This may reflect differences in toxicity grading, immunosuppressant use and hospitalization thresholds. Like other published experiences, we found that irAE severity (reflected by management of toxic effects as an outpatient or hospitalized inpatient) did not compromise the survival gains seen with irAE development. However, this finding is not universally supported.
“A single study demonstrated only high-grade irAEs in NSCLC,” they added. “In contrast, pooled data from phase 3 randomized clinical trials evaluating atezolizumab [Tecentriq, Genentech)] reported only low-grade irAEs had inferior survival except at a 12-month landmark analysis, where median OS was longer than among patients without irAEs.”
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Cook S, et al. JAMA Netw Open. 2024;doi:10.1001/jamanetworkopen.2023.52302.
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