Abstract 1050P
Background
The impact of immune related adverse events (irAEs) on melanoma outcomes is unclear. We evaluated the survival of patients (pts) with locally advanced (LA)/metastatic melanoma (MM) treated with immune checkpoint inhibitors (ICI), as well as risk factors for and impact of irAEs.
Methods
Pts ≥18 years (y) with LA/MM who received ≥1 cycle of an ICI at BC Cancer from 2012-2019 were identified using the BC Cancer Registry and Pharmacy databases. IrAEs were graded using the CTCAEv5. A landmark analysis of pts progression-free at 20 weeks was performed.
Results
451 pts were identified: cutaneous (n=329, 73% [BRAF+ = 42%]), mucosal (n=30, 7%), ocular (n=41, 9%), and unknown (n=51, 11% [BRAF+ = 33%]) subtypes. With a median follow-up of 30 months (m), 2-y overall survival (OS) was 47%, 31%, 29%, and 60% per subtype, respectively (p<0.001). Combination ipilimumab/nivolumab (ipi/nivo), PD1 inhibitor alone (PD1), and ipilimumab alone (ipi) were given to 96 (21%), 275 (61%) and 80 (18%) pts, respectively. 2-y OS was superior for ipi/nivo vs PD1 (63% vs 49%, p=0.01), and remained significant when stratified by cutaneous/unknown (62% vs 53%, p=0.05) and mucosal (73% vs 21%, p=0.025). However, this difference was only observed in males (2-y OS 69% vs 47%, p=0.001; females, p=0.9). 62% of pts had ≥1 irAE: endocrine (21%), GI (20%), and skin (34%). Grade (gr) ≥3 irAEs by treatment were 46% (ipi/nivo) vs 11% (PD1) vs 15% (ipi), (p<0.001). Vitiligo (12%) was associated with improved OS (2-y OS 84% vs 41%, p<0.001). In a landmark 20-week analysis, OS was similar by irAE development (p=0.91). Gr ≥2 irAE was associated with normal LDH (82% vs 19%, p=0.01) and sex (male 69% vs female 31%, p=0.019) in ipi/nivo, but no risk factors were identified in PD1. Steroid use ≤2m before PD1 reduced irAE risk but also OS (p<0.0001) (including M1d, 2-y OS 57% vs 26%, p=0.016), an impact not observed with ipi/nivo (p=0.927).
Conclusions
Males have a higher risk of gr ≥2 irAEs and improved OS using ipi/nivo. Steroid use before ICI was associated with reduced toxicity and efficacy of PD1 inhibitor therapy, but not in those treated with ipi/nivo. Further studies that correlate biomarkers with irAE risk and outcome across ICI therapies are needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.