دورية أكاديمية

The impact of immunosuppressive agents on immune checkpoint inhibitor efficacy in patients with advanced melanoma: A real‐world, multicenter, retrospective study.

التفاصيل البيبلوغرافية
العنوان: The impact of immunosuppressive agents on immune checkpoint inhibitor efficacy in patients with advanced melanoma: A real‐world, multicenter, retrospective study.
المؤلفون: Lev‐Ari, Shaked, Serzan, Michael, Wu, Tianmin, Ip, Andrew, Pascual, Lauren, Sinclaire, Brittany, Adams, Shari, Marafelias, Michael, Ayyagari, Lakshmi, Gill, Sarvarinder K., Ma, Barbara, Zaemes, Jacob P., Della Pia, Alexandra, Alaoui, Adil, Madhavan, Subha, Belouali, Anas, Pecora, Andrew, Ahn, Jaeil, Atkins, Michael B., Shah, Neil J.
المصدر: Cancer (0008543X); Jun2023, Vol. 129 Issue 12, p1885-1894, 10p
مصطلحات موضوعية: IPILIMUMAB, IMMUNE checkpoint inhibitors, IMMUNOSUPPRESSIVE agents, DRUG side effects, ADVERSE health care events, PROPORTIONAL hazards models
مستخلص: Background: Immune‐related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) are often managed via immunosuppressive agents (ISAs); however, their impact on ICI efficacy is not well studied. The impact of the use of ISAs on ICI efficacy in patients with advanced melanoma was therefore investigated. Methods: This is a real‐world, multicenter, retrospective cohort study of patients with advanced melanoma who received ICIs (n = 370). Overall survival (OS) and time to treatment failure (TTF) from the time of ICI initiation were compared among patients in subgroups of interest by unadjusted and 12‐week landmark sensitivity‐adjusted analyses. The association of irAEs and their management with OS and TTF were evaluated using univariate and multivariable Cox proportional hazards regression models. Results: Overall, irAEs of any grade and of grade ≥3 occurred in 57% and 23% of patients, respectively. Thirty‐seven percent of patients received steroids, and 3% received other ISAs. Median OS was longest among patients receiving both (not reached [NR]), shorter among those receiving only systemic steroids (SSs) (84.2 months; 95% CI, 40.2 months to NR), and shortest among those who did not experience irAEs (10.3 months; 95% CI, 6–20.1 months) (p <.001). Longer OS was significantly associated with the occurrence of irAEs and the use of SSs with or without ISAs upon multivariable‐adjusted analysis (p <.001). Similar results were noted with anti–programmed death 1 (PD‐1) monotherapy and combination anti–PD‐1 plus anti–cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) therapy, and with 12‐week landmark sensitivity analysis (p =.01). Conclusions: These findings in patients with melanoma who were treated with ICIs suggest that the use of SSs or ISAs for the management of irAEs is not associated with inferior disease outcomes, which supports the use of these agents when necessary. This real‐world, multicenter, retrospective study of patients with advanced melanoma who received immune checkpoint inhibitors (ICIs) suggests that the use of systemic steroids (SSs) or immunosuppressive agents (ISAs) for the management of immune‐related adverse events (irAEs) is not associated with inferior ICI efficacy, which supports their use when necessary. These data further suggest that irAEs and their management with SSs or other ISAs are predictive biomarkers of ICI efficacy. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:0008543X
DOI:10.1002/cncr.34742