Incidence, Features And Management Of Radionecrosis (Rn) In Melanoma Patients (Pts) Treated With Cerebral Radiotherapy (Rt) And Anti-Pd-1 Antibodies (Pd1).

9513 Background: Melanoma brain metastases confer poor prognosis, with various treatments used including RT and PD1. While RT and PD1 may have a synergistic effect to improve efficacy, RN may complicate RT, and whether PD1 potentiates this is unknown. We examined the incidence and features of RN and other neurotoxicities in melanoma pts treated with PD1 and whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS). Methods: Pts treated with PD1 who received WBRT/SRS during or within 1 year (y) of PD1 who survived > 1y were examined for short and long term neurotoxicity. 2 cohorts were included: (A) consecutive pts fulfilling eligibility criteria from 8 melanoma centers, (B) additional cases of RN from 3 centers. Pt demographics, disease features, treatment details, neurotoxicity, and outcome data were collected. Results: Cohort A included 118 pts, with median follow-up of 24.3 months (mo). Median age was 56yo, 51% had mutant BRAF, 41% elevated LDH and 65% were ECOG 1-2 at PD1 start. 58% had prior ipilimumab and 43% prior MAPK inhibitors. 85% were treated with pembrolizumab, 10% nivolumab and 5% combination ipilimumab/nivolumab. Most pts (82, 69%) had SRS, 22 (19%) had WBRT alone and 14 pts (12%) had both. Median PFS was 24mo and OS was 45.8mo. 21 pts (18%) developed RN, (14/82) 17% after SRS, (2/22) 9% after WBRT and (5/14) 36% after both. With 13 further cases from cohort B (total 34), all had radiological signs on MRI, 78% had neurological symptoms and 56% had pathological confirmation of RN. Median time to symptom onset and to first radiological sign was 9.8mo and 10.8mo, respectively. 52% were treated with steroids and 30% had bevacizumab, with clinical improvement in 64% and 100%, respectively. Updated analysis including clinical variables associated with RN development will be presented, including RT dose and schedule. Conclusions: RN is a significant toxicity in melanoma pts with brain metastases treated with RT and PD1, particularly in long term survivors. Further research to identify those at risk of RN, those who do not require RT, and studies exploring RT and PD1 schedules are required.