Myopathic syndromes and immune checkpoint inhibitors: A systematic review.

Abstract

e14580 Background: Though ICIs are a breakthrough in advanced cancer treatment, their side effects are often overlooked. This study identifies the prevalence and prognostic factors of ICI-associated myopathic syndromes. Methods: A systematic review (March 2023-December 2024) was conducted using MEDLINE, Cochrane, and EMBASE databases (PROSPERO- CRD42023461535). A total of 109 studies (2016-2024) with 273 eligible ICI-treated patients were analyzed. Results: Among patients evaluated for myositis, myasthenia gravis (MG), and their overlap, males predominated (73.84%), particularly in the overlap group (86.30%). Melanoma was the primary malignancy (41.77%). PD-1 inhibitors were most commonly used (63.74%), especially in myositis cases (69.44%), while combination therapies were prevalent in the overlap group (33.33%). Adverse events occurred in 46.52% of patients, with myocarditis being most frequent (76.38%), particularly in the overlap group (91.8%). Malignancy outcomes improved in 32.71% of cases, highest in MG (54.17%), though mortality peaked in the overlap group (52.00%). Post-ICI improvement was observed in 63.18% of patients, with MG showing the best response (71.79%). Univariate analysis revealed that steroid use reduced death odds (OR 0.16, 95% CI: 0.02-1.26, p<0.047), while both ocular (OR 0.45, 95% CI: 0.23-0.88, p<0.02) and generalized MG (OR 0.23, 95% CI: 0.1-0.54, p<0.001) showed lower mortality compared to other groups. Multivariate analysis demonstrated significantly lower risk in female patients (OR: 0.23, 95% CI: 0.053-0.987, p<0.048). Conclusions: This study reveals distinct risk profiles and protective factors in ICI-induced muscle adverse effects, underscoring the need for further research to optimize personalized management strategies of this emerging field. Demographics. Variables Total, n/N(%) Myositis, n/N(%) MG, n/N(%) Overlap, n/N(%) Gender (Male) 175/273 (73.84%) 84/117 (71.79%) 28/47 (59.57%) 63/73 (86.30%) Age (Median, IQR) 70 (63–75) 68 (61–75) 70 (61.5–77) 72 (65–76) Cancer (Melanoma) 99/273 (41.77%) 49/144 (34.03%) 22/49 (44.90%) 28/80 (38.36%) ICI Class - PD-1 inhibitors 174/273 (63.74%) 100/144 (69.44%) 26/49 (53.06%) 48/80 (60.00%) - PD-L1 inhibitors 36/273 (13.19%) 15/144 (10.42%) 6/49 (12.24%) 15/80 (18.75%) - PD-1 + CTLA-4 inhibitors 53/273 (19.41%) 27/144 (18.75%) 11/49 (22.45%) 15/80 (18.75%) Associated AEs - Myocarditis 97/127* (76.38%) 41/63 (65.10%) 11/15 (73.33%) 45/49 (91.80%) Malignancy Outcome - Improved/ Stable 44/107* (41.12%) 30/58 (51.72%) 17/24 (70.84%) 7/35(28.00%) - Died/ Deteriorated 53/107* (49.53%) 28/58 (48.28%) 7/24 (29.17%) 28/35 (72.00%) ICI Therapy Outcome - Improved/ Stable 134/201* (66.66%) 76/110 (69.09%) 28/39 (71.79%) 30/52 (57.69%) - Died/ Deteriorated 67/201* (33.33%) 34/110 (30.91%) 11/39 (28.21%) 22/52 (42.28%) *Not all studies included the required variables.