Single-Agent Vincristine Sulfate Liposomes Injection (Marqibo^®) Compared to Historical Single-Agent Therapy for Adults with Advanced, Relapsed and/or Refractory Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia

Abstract 2592

There are no standard of care or approved treatments specifically for advanced, relapsed and/or refractory adult Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL). Pronounced toxicity of multi-agent salvage therapy, residual toxicity in heavily pre-treated subjects, and poor response to prior multi-agent therapy including hematopoietic stem cell transplant (HSCT) may prompt the use of single-agent salvage including investigational agents. We compared the efficacy and early plus induction (30-day) mortality rates for single-agent weekly intravenous vincristine sulfate liposomes injection (VSLI, Marqibo^®) 2.25 mg/m² (no dose cap) in adults with Ph- ALL in second or greater relapse or that had progressed following 2 or more lines of anti-leukemia therapy (RALLY Study, N=65) with those from the not previously described, single-agent (non-VSLI), second salvage, Ph- ALL subpopulation (N=56) from a large published report (O'Brien et al, Cancer 2008; 113:3186–91). Despite inclusion of subjects requiring third and greater salvage therapy in the RALLY Study, the O'Brien single-agent population represents the best historical comparator to the RALLY Study population. The most common of the 28 different agents used in the O'Brien study were vinorelbine (6), clofarabine (5), nelarabine (4), and topotecan (4). No subject in the O'Brien study received single-agent standard vincristine sulfate as second salvage. The table below highlights key characteristics of the two ALL populations as well as key efficacy and toxicity outcomes.

Overall, the RALLY Study population was more advanced and heavily pre-treated than the O'Brien population. Despite the poorer prognosis, universal prior standard vincristine exposure, and majority of subjects requiring fourth or greater line therapy, single-agent VSLI 2.25 mg/m² (no dose cap) resulted in a higher complete response (CR+CRi) rate, complete plus partial response (PR) rate, median complete response duration (* no median was calculated for the O'Brien Population because there were only 2 responders), and overall survival duration than was observed with a variety of third-line single-agent adult Ph- ALL salvage therapies. The median overall survival durations for the RALLY Study subjects achieving CR (7), CRi (6), and PR (6) were comparable. The majority of RALLY Study complete responders had a remission duration sufficient to facilitate a subsequent, and potentially curative HSCT. In fact, 12 (18.5%) of the 65 subjects in the RALLY Study were able to undergo a post-VSLI HSCT and 5 (7.7%) subjects were long-term survivors (post-VSLI survival greater than 1 year). Single-agent VSLI was associated with a more favorable early plus induction (30-day) mortality rate in the RALLY Study than observed in relation to other single-agent therapies. Single-agent weekly VSLI 2.25 mg/m2 has the potential to provide a relatively safe and effective induction treatment and “bridge” to HSCT compared to historical non-VSLI single-agent therapies.