Study Highlights Importance of Reporting Data on Multiorgan Toxicities

A study published in the Journal of the National Comprehensive Cancer Network suggested that among clinical trials in which patients with non-small cell lung cancer (NSCLC) were treated with atezolizumab (Tecentriq), multiorgan immune-related adverse events (irAEs) were reported in 5.4%.¹

Given this finding, researchers indicated that future trial reporting should consider the incorporation of data on multiorgan toxicities in addition to single-organ specific toxicities.

“Multi-organ irAEs are under-recognized, under reported, and their pathophysiology is poorly understood,” lead researcher Ganessan Kichenadasse, MBBS, FRACP, of the Flinders Centre for Innovation in Cancer at Flinders University in Bedford Park, Australia, said in a press release.² “We need a concerted international effort to improve our understanding and help identify predisposing factors and prevention strategies. Treating teams should be aware of the potential for irAEs which affect multiple organs and institute plans for recognizing and managing them.”

In order to determine the incidence, time of onset, and risk factors for multiorgan irAEs, researchers conducted a post hoc pooled analysis using individual patient data from atezolizumab monotherapy arms of 4 NSCLC clinical trials. From a total of 1548 patients identified, 730 irAE episodes were reported in 424 patients (27%). Skin irAEs were most often reported (42%), followed by laboratory abnormalities (27%) and endocrine (11.6%), neurologic (7.6%), and pulmonary (6.2%) irAEs.

Overall, 84 patients (5.4%) had multiorgan irAEs, including 70 with 2, 13 with 3, and 1 with 4 different organs affected. Moreover, “skin plus” or “laboratory plus” were the most commonly observed irAE multiorgan clusters.

Notably, patients with multiorgan irAEs were more likely to be white and have a good performance status, a lower baseline neutrophil-lymphocyte ratio, and a good or intermediate lung immune prognostic index score. In addition, multiorgan irAEs were also correlated with improved overall survival (HR, 0.47; 95% CI, 0.28-0.78; P < .0001) but not with progression-free survival (HR, 0.92; 95% CI, 0.62-1.35; P = .74) compared with patients who had no irAEs.

“This study confirms that more than 1 organ, at the same time or sequentially, can be affected by immune-related adverse events from checkpoint inhibitor therapy,” Igor Puzanov, MD, MSci, FACP, professor of Medicine, director of the Early Phase Clinical Trials Program, and chief of Melanoma at Roswell Park Comprehensive Cancer Center, who was not involved in this study, said in the release. “This is worth noting for all practicing oncologists and other specialists taking care of patients who are receiving these therapies. The silver lining here is the seemingly improved overall survival we see among these patients.”

Importantly, researchers noted this analysis was a post hoc exploratory analysis and should therefore be considered hypothesis-generating and confirmed in other studies. Moreover, these data were specifically from lung cancer trials of atezolizumab, and it remains unclear whether a similar pattern of multiorgan irAEs occurs in other cancer types or with other immune checkpoint inhibitors.

References:

1. Kichenadasse G, Miners JO, Mangoni AA, Rowland A, Hopkins AM, Sorich MJ. Multiorgan Immune-Related Adverse Events During Treatment With Atezolizumab. Journal of the National Comprehensive Cancer Network. doi: 10.6004/jnccn.2020.7567

2. New Research in JNCCN Sheds Light on Multi-Organ Adverse Events from Immunotherapy [news release]. Plymouth Meeting, PA. Published September 8, 2020. Accessed September 16, 2020. https://www.eurekalert.org/pub_releases/2020-09/nccn-nri090420.php