(ChemotherapyAdvisor) – Use of high-dose vincristine sulfate liposome injection (VSLI) monotherapy in patients with advanced Philadelphia chromosome (Ph)–negative acute lymphoblastic leukemia (ALL) resulted in “meaningful clinical outcomes” that included durable responses and bridging to hematopoietic cell transplantation (HCT), results of a pivotal, phase 2, multinational trial reported in the Journal of Clinical Oncology online November 19.

VSLI, sphingomyelin, and cholesterol nanoparticle vincristine (VCR) facilitates VCR dose-intensification and densification plus enhances target tissue delivery, noted corresponding author Steven R. Deitcher, MD, of Talon Therapeutics, South San Francisco, CA, and colleagues.

The study evaluated VSLI monotherapy in 65 adults with (Ph)–negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once weekly “until response, progression, toxicity, or pursuit of HCT,” they wrote. Primary end point was complete response (CR) or CR with incomplete hematologic recovery (CRi).

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The CR/CRi rate was 20%; overall response rate was 35%. “VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies,” Dr. Deitcher reported. Median duration of CR/CRi was 23 weeks (range, 5 to 66 weeks). Twelve patients bridged to a post-VSLI HCT, and 5 patients were long-term survivors.

VSLI was associated with a 30-day mortality rate of 12%. The toxicity profile was “predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR,” they wrote.

“Phase 3 studies in frontline adult ALL and frontline aggressive non-Hodgkin lymphoma, predicated on the current study and the successful combination of VSLI with other chemotherapies and rituximab in other phase II studies, are currently enrolling,” the authors concluded.

The study was supported by Talon Therapeutics.