High-Dose Vincristine Sulfate Liposome Injection (Marqibo®) Is Not Associated With Clinically Meaningful Hematologic Toxicity

Abstract Background The treatment of hematologic malignancy patients with heavily pre-treated, advanced, relapsed, or refractory disease and those with advanced age, active infection, cardiovascular disease, recent surgery, or poor performance status may require therapies with limited hematologic toxicity and associated peripheral blood cytopenias. Cancer and concomitant chemotherapy related anemia, neutropenia, and thrombocytopenia in patients with hematologic malignancy complicate evaluation of hematologic toxicity related to new drugs. Vincristine sulfate liposome injection (VSLI; Marqibo®) is a new drug developed to optimize vincristine (VCR) pharmacokinetics and facilitate VCR dose-intensification and densification. VSLI is active in untreated and relapsed lymphomas, and was recently approved in the United States for relapsed and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. Methods We assessed the hematologic toxicity of VSLI 2.25 mg/m2 administered every 14 days (Cohort 1) or 7 days (Cohort 2) in 54 patients with metastatic uveal melanoma, a cancer not known to involve the bone marrow. Cohort 1 patients could have received 1 prior systemic therapy. Cohort 2 patients must not have received any prior systemic chemotherapy, immunotherapy, cancer vaccine, or hepatic arterial chemotherapy for metastatic disease. Results Patients in Cohort 2 received a higher median number of VSLI doses (6 vs. 4) over a shorter median time period (5.7 weeks vs. 8.7 weeks) resulting in a larger median cumulative exposure (22.6 mg vs. 17.7 mg) and near doubling of median dose density (4.0 mg/week vs. 2.2 mg/week) compared to patients in Cohort 1. Despite greater VSLI exposure and dose density, Cohort 2 had a smaller decrease from baseline in median neutrophil count and greater increase from baseline in median platelet count compared to Cohort 1. Both Cohorts experienced similar gradual decreases in hemoglobin concentration over time that were attributed to cancer-associated anemia and frequent blood sampling. Hematologic adverse events (AEs) were uncommon and mostly Grade 1 or 2. There were no Grade 4 hematologic AEs. Conclusions VSLI at its approved dose resulted in a low incidence of clinically meaningful hematologic toxicity. A near doubling of median dose density did not have an impact on the reported incidence and severity of hematologic AEs. VSLI may be well suited for use alone or in combination with myelosuppresive drugs and in patients unable to tolerate peripheral blood cytopenias. Disclosures: Silverman: Talon Therapeutics: Employment. Deitcher:Talon Therapeutics: Employment, Equity Ownership.