Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma. Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507. Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached. Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted

Medical Oncology Follow-Up and Adjuvant Therapies

Second part of presentation continues here

Safety of Lobar Hepatic Arterial Embolization in Metastatic Uveal Melanoma Patients with Underlying Gilbert\u27s Disease

Introduction ❖ Uveal melanoma is the most common primary intraocular malignant tumor in adults. ❖ Up to half of all patients develop systemic metastases, with liver involvement in \u3e90% of patients.1 ❖ Various liver-directed, locoregional therapies (i.e. chemoembolization, immunoembolization, radioembolization, and ablation) have played a significant role in prolonging the lives of patients with metastatic uveal melanoma.2 ❖ Elevated bilirubin levels are typically considered a relative contraindication for lobar hepatic arterial embolization treatment, given mainly the increased risk of precipitating hepatic failure. ❖ Gilbert\u27s syndrome, also known as benign unconjugated hyperbilirubinemia, is a hereditary disorder of bilirubin conjugation. Gilbert’s syndrome leads to elevated levels of serum bilirubin, that do not truly reflect cholestasis or liver failure and therefore should not exclude patients from targeted embolization therapy.3 Poster presented at: World Conference on Interventional Oncology in Boston MA.https://jdc.jefferson.edu/medoncposters/1003/thumbnail.jp