ET-53IPILIMUMAB FOR RECURRENT GLIOBLASTOMA (GBM)

Available treatments for recurrent glioblastoma (GBM) are inadequate, and median survival is approximately 6 months. Ipilimumab (ipi) is an immune modulator that inhibits CTLA-4 and is active in refractory melanoma, including brain metastases. We retrospectively reviewed records of patients treated with ipi for recurrent GBM, and explored safety, response, and survival using Kaplan-Meier methodology. There were 10 patients (6 men), median age 55 years (range 41-65). All received prior radiotherapy and temozolomide, and 9 received prior bevacizumab. Ipi (3mg/kg/dose) was administered for 1st (1), 2nd (4), 3rd (4), or 6th (1) recurrence. Bevacizumab was administered concurrently to all patients to reduce corticosteroid requirements that can blunt ipi effect. Other concurrent therapies included GM-CSF (8), nitrosoureas (5), carboplatin (1), temozolomide (1), or lapatinib (1). Corticosteroids (dexamethasone, 0.75 - 4.0 mg/day) were administered concurrently in 4. All patients were evaluated for toxicity. One experienced fever, elevated LDH, and transaminitis. One experienced rash and fatigue. There were no other significant toxicities, specifically no endocrinopathies or electrolyte abnormalities. Responses included stable disease (5) and progressive disease (5). Median progression-free survival (PFS) was 2.8 months and overall survival (OS) was 5.1 months, although 5 patients remain alive. Results were the same for those (9) treated for bevacizumab-refractory disease. Historical control suggests results are similar in bevacizumab-failure patients treated with salvage chemotherapy (PFS 1-3 moths, OS 4-6 months), and superior to those in patients who receive no further treatment following progression on bevacizumab. Comparison of immunologic effects in pre-ipi and post-ipi tumor tissue for one case is underway. Ipi can be administered safely to patients with GBM concurrently with GM-CSF, bevacizumab, nitrosoureas, and other therapies. In patients treated for bevacizumab-refractory disease, ipi may prolong PFS and OS as compared to historical controls. Concurrent bevacizumab may reduce corticosteroid requirements. Treatment earlier in the disease course merits investigation.