High-Dose Vincristine Sulfate Liposome Injection, for Advanced, Relapsed, or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in an Adolescent and Young Adult Subgroup of a Phase 2 Clinical Trial

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/m(2) 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).