NYMC Faculty Publications

High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

Author Type(s)

Faculty

DOI

10.1200/JCO.2012.46.2309

Journal Title

Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology

First Page

676

Last Page

683

Document Type

Article

Publication Date

2-20-2013

Department

Medicine

Keywords

Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Phytogenic, Constipation, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Resistance, Neoplasm, Female, Humans, Injections, Intravenous, Liposomes, Male, Middle Aged, Nervous System Diseases, Neutropenia, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence, Remission Induction, Survival Analysis, Treatment Outcome, Vincristine, Young Adult

Disciplines

Medicine and Health Sciences

Abstract

PURPOSE: Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) -negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT).

PATIENTS AND METHODS: Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m(2), without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi).

RESULTS: The CR/CRi rate was 20% and 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. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%).

CONCLUSION: High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR.

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