PMID- 35315916 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20231213 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 5 IP - 3 DP - 2022 Mar 1 TI - Immune-Related Adverse Events After Immune Checkpoint Inhibitors for Melanoma Among Older Adults. PG - e223461 LID - 10.1001/jamanetworkopen.2022.3461 [doi] LID - e223461 AB - IMPORTANCE: Immune checkpoint inhibitors (ICIs) have improved survival in patients with advanced melanoma but can be associated with a spectrum of immune-related adverse events (AEs), including both autoimmune-related AEs and other immune-related inflammatory AEs. These associations have primarily been evaluated in clinical trials that include highly selected patients, with older adults often underrepresented. OBJECTIVE: To evaluate the association between use of ICIs and immune-related AEs (autoimmune and other immune related) among older patients with cutaneous melanoma. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study was conducted from January 1, 2011, to December 31, 2015. Data were analyzed from January 31 to May 31, 2021. With use of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries, patients of White race diagnosed with stages II-IV or unknown (American Joint Committee on Cancer, AJCC Cancer Staging Manual 6th edition) first primary cutaneous melanoma during 2011-2015, as reported to SEER, and followed up through December 31, 2015, were identified. EXPOSURES: Immune checkpoint inhibitors for treatment of melanoma. MAIN OUTCOMES AND MEASURES: The association between ICIs and immune-related AEs ascertained from Medicare claims data was estimated using multivariable Cox regression with hazard ratios (HRs) and 95% CIs and with cumulative incidence accounting for competing risk of death. RESULTS: The study included 4489 patients of White race with first primary melanoma (3002 men [66.9%]; median age, 74.9 [range, 66.0-84.9] years). During follow-up (median, 1.4 [range, 0-5.0] years), 1576 patients (35.1%) had an immune-related AE on a Medicare claim. Use of ICIs (reported for 418 patients) was associated with autoimmune-related AEs (HR, 2.5; 95% CI, 1.6-4.0), including primary adrenal insufficiency (HR, 9.9; 95% CI, 4.5-21.5) and ulcerative colitis (HR, 8.6; 95% CI, 2.8-26.3). Immune checkpoint inhibitors also were associated with other immune-related AEs (HR, 2.2; 95% CI, 1.7-2.8), including Cushing syndrome (HR, 11.8; 95% CI, 1.4-97.2), hyperthyroidism (HR, 6.3; 95% CI, 2.0-19.5), hypothyroidism (HR, 3.8; 95% CI, 2.4-6.1), hypopituitarism (HR, 19.8; 95% CI, 5.4-72.9), other pituitary gland disorders (HR, 6.0; 95% CI, 1.2-30.2), diarrhea (HR, 3.5; 95% CI, 2.5-4.9), and sepsis or septicemia (HR, 2.2; 95% CI, 1.4-3.3). Most associations were pronounced within 6 months following the first ICI claim and comparable with or without a baseline history of autoimmune disease. The cumulative incidence at 6 months following the first ICI claim was 13.7% (95% CI, 9.7%-18.3%) for autoimmune-related AEs and 46.8% (95% CI, 40.7%-52.7%) for other immune-related AEs. CONCLUSIONS AND RELEVANCE: In this cohort study of older adults with melanoma, ICIs were associated with autoimmune-related AEs and other immune-related AEs. Although some findings were consistent with clinical trials of ICIs, others warrant further investigation. As ICI use continues to expand rapidly, ongoing investigation of the spectrum of immune-related AEs may optimize management of disease in patients. FAU - Schonfeld, Sara J AU - Schonfeld SJ AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. FAU - Tucker, Margaret A AU - Tucker MA AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. FAU - Engels, Eric A AU - Engels EA AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. FAU - Dores, Graca M AU - Dores GM AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. AD - Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland. FAU - Sampson, Joshua N AU - Sampson JN AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. FAU - Shiels, Meredith S AU - Shiels MS AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. FAU - Chanock, Stephen J AU - Chanock SJ AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. FAU - Morton, Lindsay M AU - Morton LM AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20220301 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Immune Checkpoint Inhibitors) SB - IM MH - Aged MH - Cohort Studies MH - Humans MH - Immune Checkpoint Inhibitors/adverse effects MH - Male MH - Medicare MH - *Melanoma/drug therapy MH - *Skin Neoplasms/drug therapy MH - United States/epidemiology MH - Melanoma, Cutaneous Malignant PMC - PMC8941351 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2022/03/23 06:00 MHDA- 2022/04/15 06:00 PMCR- 2022/03/22 CRDT- 2022/03/22 12:11 PHST- 2022/03/22 12:11 [entrez] PHST- 2022/03/23 06:00 [pubmed] PHST- 2022/04/15 06:00 [medline] PHST- 2022/03/22 00:00 [pmc-release] AID - 2790182 [pii] AID - zoi220131 [pii] AID - 10.1001/jamanetworkopen.2022.3461 [doi] PST - epublish SO - JAMA Netw Open. 2022 Mar 1;5(3):e223461. doi: 10.1001/jamanetworkopen.2022.3461.