High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult philadelphia chromosome-negative acute lymphoblastic leukemia

Susan O'Brien, Gary Schiller, John Lister, Lloyd Damon, Stuart Goldberg, Walter Aulitzky, Dina Ben-Yehuda, Wendy Stock, Steven Coutre, Dan Douer, Leonard T. Heffner, Melissa Larson, Karen Seiter, Scott Smith, Sarit Assouline, Philip Kuriakose, Lori Maness, Arnon Nagler, Jacob Rowe, Markus SchaichOfer Shpilberg, Karen Yee, Guenter Schmieder, Jeffrey A. Silverman, Deborah Thomas, Steven R. Deitcher, Hagop Kantarjian

Research output: Contribution to journalArticle

127 Scopus citations

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 highdose 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/m2, 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.

Original languageEnglish (US)
Pages (from-to)676-683
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number6
DOIs
StatePublished - Feb 20 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    O'Brien, S., Schiller, G., Lister, J., Damon, L., Goldberg, S., Aulitzky, W., Ben-Yehuda, D., Stock, W., Coutre, S., Douer, D., Heffner, L. T., Larson, M., Seiter, K., Smith, S., Assouline, S., Kuriakose, P., Maness, L., Nagler, A., Rowe, J., ... Kantarjian, H. (2013). High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult philadelphia chromosome-negative acute lymphoblastic leukemia. Journal of Clinical Oncology, 31(6), 676-683. https://doi.org/10.1200/JCO.2012.46.2309