Timing of palliative care referral and overall survival in patients with melanoma brain metastases treated with ipilimumab and nivolumab.

Abstract

e21607 Background: The association between timing of palliative care referral and survival outcomes in patients with melanoma brain metastases (MBM) treated with immune checkpoint inhibitors remains poorly characterized. Methods: We conducted a retrospective cohort study of patients with MBM treated with combination ipilimumab and nivolumab at Mayo 3 sites from 2016 to 2024. Palliative care referral timing relative to MBM diagnosis was categorized as early (≤56 days), late ( > 56 days), or none. Patients without referral documentation were excluded from referral-based analyses. Overall survival (OS) was estimated using Kaplan–Meier methods and compared with log-rank tests. Multivariable Cox proportional hazards models were used to identify factors independently associated with OS, with stepwise selection (entry p < 0.25; stay p < 0.15). Results: Among 147 patients, 139 had referral information: 33 (23.7%) early, 56 (40.3%) late, and 50 (36.0%) no referral. Median OS differed significantly by referral timing (log-rank p < 0.0001): 2.8 months (early), 7.9 months (late), and 47.8 months (no referral). Among patients with ECOG 2–3, a higher proportion had early or late referral (each 42.9%) compared with no referral (14.3%), whereas patients with ECOG 0–1 were more evenly distributed across referral groups (early 21.6%, late 40.0%, none 38.4%). In multivariable analysis of 88 patients with complete covariate data, both early (HR 4.54; p = 0.0016) and late referral (HR 2.86; p = 0.011) were independently associated with worse OS compared with no referral. Progressive disease versus objective response (HR 4.45; p = 0.0002), hemorrhagic metastases (HR 2.79; p = 0.0015), male sex (HR 2.07; p = 0.044), and increasing age (HR 1.02 per year; p = 0.032) were also associated with inferior OS. Treatment with ipilimumab 1 mg/kg plus nivolumab 3 mg/kg showed a trend toward improved OS compared with ipilimumab 3 mg/kg plus nivolumab 1 mg/kg (HR 0.48; p = 0.055). Conclusions: Timing of palliative care referral was strongly associated with overall survival in patients with MBM treated with ipilimumab and nivolumab. Although patients with ECOG 2–3 were more frequently referred early or late, ECOG category overall did not clearly differentiate referral timing groups, suggesting referral may reflect unmeasured clinical factors beyond baseline performance status. Prospective studies incorporating more granular functional and symptom measures are needed to better define the role of palliative care integration in this population. Multivariable cox model for overall survival. Variable Comparison HR P value Referral timing Early vs None 4.54 0.0016 Late vs None 2.86 0.011 Best overall response PD vs ORR 4.45 0.0002 SD vs ORR 2.16 0.098 Hemorrhagic metastases Yes vs No 2.79 0.0015 Sex Male vs Female 2.07 0.044 Age Per year increase 1.02 0.032 Regimen Ipi1+Nivo3 vs Ipi3+Nivo1 0.48 0.055