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Patients with autoimmune disease receiving ICI exhibit better survival vs. controls


September 01, 2022

2 min read

Disclosures:
The MelBase cohort is sponsored by the French National Cancer Institute, Bristol Myers Squibb, MSD, Novartis and Roche. Placais reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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Although they exhibit a greater risk for severe immune-related adverse effects, patients with preexisting autoimmune disease receiving immune checkpoint inhibitors for melanoma had better 2-year survival than controls, according to data.

Immune checkpoint inhibitors (ICIs) are one of the major therapeutic advances in oncology in the past 10 years,” Léo Plaçais, MD, of the internal medicine and clinical immunology department at Hopital Bicêtre, in France, and co-authors wrote in the Annals of the Rheumatic Diseases. “Since their first approval in metastatic melanoma and non-small cell lung cancer (NSCLC), ICI indications have broadened and now extend to more than 50 different cancer types.

Graphic showing data from the results section
Although they exhibit a greater risk for severe immune-related adverse effects, patients with preexisting autoimmune disease receiving immune checkpoint inhibitors for melanoma had better 2-year survival than controls, according to data derived from Placais L, et al. Ann Rheum Dis. 2022;doi:10.1136/ard-2022-222186.

“However, as these pathways are physiologically involved in the downregulation of T cell responses and act as gatekeepers to prevent excessive T-cell activation, ICIs subsequently expose to the risk of T-cell-driven autoimmunity,” they added.

To study the prevalence of immune-related adverse events (irAEs) in patients with preexistng autoimmune diseases receiving ICIs in stage 3 or 4 melanoma, Plaçais and colleagues conducted a longitudinal, multicenter, prospective study using the MelBase cohort. The cohort follows patients from 26 medical sites receiving treatment for unresectable stage 3 or 4 melanoma, collecting data on disease progression, treatment records and adverse events, as well as the strategies used to handle them. The database also includes demographic information including age, sex and medical history.

Patients aged 18 years or older with tumor availability for historical validation and the absence of prior systemic treatment, aside from adjuvant therapy, were available for inclusion. During enrollment, the physician in charge of the included patients declared whether the patient had a history of autoimmune disease. The decision to initiate ICIs was made by a multidisciplinary board specializing in immunotoxicity management.

Immune-related adverse events were defined as a laboratory or event abnormality reported as “possibly, probably or certainly linked” to immunotherapy, the researchers wrote. Clinical subtypes for irAEs were grouped as cardiovascular, endrocrinological, rheumatological, cutaneous, pulmonary, hematological, neurological, psychiatric, renal, ophthalmological, musculoskeletal and general symptoms.

A total of 110 patients with preexisting autoimmune diseases were included in the study, as were 330 controls. The study was conducted from March 2013 through October 2020. The median follow-up period was 7.2 months in test patients and 6.9 months in control patients.

Compared with control individuals, patients with preexisting autoimmune disease demonstrated an OR of 1.91 (95% CI, 1.56-2.27) for developing all-grade irAEs, and an OR of 1.44 (95% CI, 1.08-1.82) for developing irAEs of grade three or higher. Additionally, patients with preexisting autoimmune diseases had a higher chance of developing multiple adverse events (OR = 1.46; 95% CI, 1.15-2.67). However, there was no difference in irAE-related mortality between the groups, and a landmark analysis suggested better survival at 24 months among those with preexisting autoimmune diseases (P = .02), according to the researchers.

“Overall, while our results pinpoint an increased risk of irAEs and severe irAEs in patients with pAID, we did not find an increased risk of lethal irAEs and reported an increased overall survival when compared with controls, further confirming they should be considered for ICI therapy,” Plaçais and colleagues wrote. “Patients with pAID should, however, be closely monitored for irAEs, which are more frequent and occur earlier.”



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