Leptomeningeal disease (LMD) is a challenging complication of late-stage malignant melanoma with little response to systemic ICB therapy. Oliva and Ferguson et al. studied for the first time the safety and potential efficacy of direct intrathecal (IT) administration of anti-PD-1 in heavily pre-treated (including ICB-treated) melanoma patients with LMD. IT treatment alone (for cycle 1) revealed only self-limiting grade 1 or 2 toxicities, and the addition of systemic treatment in later cycles showed only expected toxicities. Median OS was 4.9 months, with 8 of 25 treated patients still alive at data lock. Evidence of durable symptomatic or imaging improvement was seen in some patients.
Contributed by Ed Fritsch
ABSTRACT: There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50mg (with IV nivolumab 240mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256 .
Author Info: (1) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. icglitza@mdanderson.org. (2) Department of Neurosurgery, The Unive
Author Info: (1) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. icglitza@mdanderson.org. (2) Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (3) Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (4) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (5) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (6) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (7) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (8) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (9) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (10) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (11) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (12) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (13) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (14) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (15) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (16) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (17) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (18) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (19) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (20) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (21) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (22) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (23) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (24) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (25) Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (26) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (27) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (28) Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (29) Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (30) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (31) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (32) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (33) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
