Gary J Schiller1, Lloyd E Damon2, Steven E Coutre3, Pamela Hsu4, Gajanan Bhat4, Dan Douer5. 1. 1 Department of Hematology, Oncology, David Geffen School of Medicine at University of California Los Angeles , Los Angeles, California. 2. 2 Department of Hematology and Blood and Marrow Transplant, University of California San Francisco , San Francisco, California. 3. 3 Department of Hematology, Stanford Cancer Institute, Stanford University School of Medicine , Stanford, California. 4. 4 Department of Clinical Science, Spectrum Pharmaceuticals , Irvine, California. 5. 5 Division of Hematology, University of Southern California , Los Angeles, California.
Abstract
PURPOSE: A study of vincristine sulfate (VCR) liposome injection (VSLI) was conducted in patients with advanced, relapsed, or refractory, Philadelphia chromosome-negative acute lymphoblastic/lymphocytic leukemia (ALL). A retrospective subgroup analysis of the results was performed to evaluate the safety and efficacy of VSLI in the adolescent and young adult (AYA) patients. METHODS: Of the 65 patients treated in the pivotal Phase 2 Study HBS407 (NCT00495079), 44 patients were aged ≤39 years (median 27 [range 19-39] years) and were included in this analysis. Patients received VSLI (2.25 mg/m2 intravenously every 7 ± 3 days) without dose capping or concurrent steroid administration in continuous 28-day cycles. RESULTS: VSLI was well tolerated in the AYA patients over a median of 5 (range 1-15) doses administered. One-third of patients (36%) experienced treatment-related serious adverse events (AEs) with peripheral neuropathy (7%), tumor lysis syndrome (7%), and febrile neutropenia (5%) in >1 patient. Neuropathy-associated AEs occurred in 82% patients; no neuropathy-related deaths occurred. The rate of complete remission (CR) (with or without complete blood count recovery) by investigator assessment was 25% in AYA patients, and the overall response rate was 39%. Median leukemia-free survival in AYA patients attaining CR was 135 (range 32-463) days, and median overall survival was 141 (range 13-620) days. CONCLUSION: VSLI provided a meaningful clinical benefit to AYA patients with ALL, and its safety profile was comparable to that of VCR despite the delivery of higher doses (individual and cumulative).
PURPOSE: A study of vincristine sulfate (VCR) liposome injection (VSLI) was conducted in patients with advanced, relapsed, or refractory, Philadelphia chromosome-negative acute lymphoblastic/lymphocytic leukemia (ALL). A retrospective subgroup analysis of the results was performed to evaluate the safety and efficacy of VSLI in the adolescent and young adult (AYA) patients. METHODS: Of the 65 patients treated in the pivotal Phase 2 Study HBS407 (NCT00495079), 44 patients were aged ≤39 years (median 27 [range 19-39] years) and were included in this analysis. Patients received VSLI (2.25 mg/m2 intravenously every 7 ± 3 days) without dose capping or concurrent steroid administration in continuous 28-day cycles. RESULTS: VSLI was well tolerated in the AYA patients over a median of 5 (range 1-15) doses administered. One-third of patients (36%) experienced treatment-related serious adverse events (AEs) with peripheral neuropathy (7%), tumor lysis syndrome (7%), and febrile neutropenia (5%) in >1 patient. Neuropathy-associated AEs occurred in 82% patients; no neuropathy-related deaths occurred. The rate of complete remission (CR) (with or without complete blood count recovery) by investigator assessment was 25% in AYA patients, and the overall response rate was 39%. Median leukemia-free survival in AYA patients attaining CR was 135 (range 32-463) days, and median overall survival was 141 (range 13-620) days. CONCLUSION: VSLI provided a meaningful clinical benefit to AYA patients with ALL, and its safety profile was comparable to that of VCR despite the delivery of higher doses (individual and cumulative).