Sex differences in tolerability to Anti-PD1 therapy: Are we all equal?

Abstract

9547 Background: Immune related adverse events (IRAEs) have emerged as a serious clinical problem in the use of immune checkpoint inhibitors. The etiology and risk factors for these potentially life-threatening adverse events remain unknown. Therefore, we assessed sex differences in tolerability to anti-PD1 therapy. Methods: All patients (pts) with metastatic melanoma treated with anti-PD1 therapy at Mayo Clinic Rochester from 2014 to 2017 were reviewed. Ocular melanoma cases were excluded. Kaplan-Meier method was used for time-to-event analysis. Results: 245 pts were identified, 148 (60%) were men, 30 (12%) were premenopausal (Pre-M) (≤52 years) and 67 (27%) were postmenopausal (Post-M) women. Baseline characteristics were similar among groups (Table 1). Pre-M women were more likely to experience IRAEs compared to Post-M women and men (67% vs. 60% vs. 46%, p < 0.04). In 23% of Pre-M women anti-PD1 therapy was discontinued due to irAE (men 12%). Pre-M women were more likely to experience endocrinopathies (35% vs. 10%, p < 0.02) and cutaneous reactions (25% vs. 15%, p < 0.02) compared to men. All cases of diabetic ketoacidosis were observed in Pre-M women (n = 6). No differences in grade ≥3 toxicities were seen across groups. Pts with IRAEs were more likely to have a radiographic response to anti-PD1 therapy regardless of sex (68% vs. 44%, p < 0.002). There was a trend towards better PFS in men with IRAEs compared to men without IRAEs (16.5 months vs. 9.7 months, p < 0.05). Conclusions: Pre-M Women were more likely to experience IRAEs compared to Post-M women and men. An association between IRAEs and response to therapy was also observed. Larger studies are needed to confirm these results and investigate etiologic mechanisms underlying these associations. Characteristics Pre-M % (n) Post-M % (n) Men % (n) p value Liver metastasis 33 (10) 33 (22) 30 (45) 0.91 Lung metastasis 47 (14) 30 (20) 42 (62) 0.16 Prior GM-CSF 43 (13) 27 (18) 18 (27) 0.01 Prior radiation 37 (11) 54 (36) 59 (87) 0.08 Prior chemotherapy 13 (4) 16 (11) 18 (27) 0.79 IRAEs 67 (20) 60 (40) 46 (68) 0.04 ≥3 grade IRAEs 50 (10) 43 (17) 31 (21) 0.12 Discontinuation of anti-PD1 due to toxicity 23 (7) 15 (10) 12 (18) 0.37