medwireNews: Researchers have identified an association between the development of multisystem immune-related adverse events (irAEs) and improved survival outcomes in immune checkpoint inhibitor (ICI)-treated patients with advanced non-small-cell lung cancer (NSCLC).
“Although patients with multisystem irAEs received a longer ICI treatment course, the association between irAE count and improved survival is sustained after adjusting for ICI duration, suggesting that these patients experience greater therapeutic effect and higher irAE risk,” writes the team in JAMA Oncology.
The study authors explain that “[a]lthough meta-analyses and systematic reviews have characterized single irAEs that occur from ICIs, there is a paucity of data regarding multisystem irAEs.”
They therefore analyzed the medical records of 623 patients with stage III–IV NSCLC who were treated with PD-1 or PD-L1 inhibitors, either as a single agent or in a combination, at one of five academic centers between January 2007 and January 2019.
Nine percent of patients experienced a multisystem irAE, most commonly pneumonitis thyroiditis, observed in seven patients, followed by hepatitis thyroiditis and dermatitis pneumonitis in five individuals each, and dermatitis thyroiditis in four. And 24% of the patients developed a single irAE.
Median progression-free survival (PFS) differed significantly between individuals who developed multisystem, single, or no irAEs, at 10.9, 5.1, and 2.8 months, respectively, and at the 1-year mark, a respective 44%, 28%, and 16% remained progression-free.
Multivariable analysis accounting for confounders such as age, sex, race, tumor histology and stage, and ICI treatment duration showed a significant 61% decrease in the risk for progression or death in the multisystem versus no irAEs group, while the risk was reduced by a significant 32% in the single irAE group.
Overall survival (OS) was similarly prolonged among patients who developed multisystem irAEs, at a median of 21.8 months compared with 12.3 and 8.7 months for those who developed a single and no irAEs, respectively.
Multisystem irAEs were associated with a significant 43% decrease in the risk for death versus no irAEs, but there was no significant association between the development of single irAEs and mortality risk, report Jarushka Naidoo (Beaumont Hospital, Dublin, Ireland) and fellow investigators.
They add that sensitivity analyses, such as those using multisystem irAEs as a time-varying covariate or restricting to individuals who received single-agent ICI therapy, “demonstrated results consistent with our main analysis.”
Naidoo et al note that “[t]he small percentage of the cohort that developed multisystem irAEs and its retrospective nature are limitations of this study,” and they “acknowledge that these data may only be generalizable to similar populations.”
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