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

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

171 ציטוטים ‏(Scopus)

תקציר

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.

שפה מקוריתאנגלית
עמודים (מ-עד)676-683
מספר עמודים8
כתב עתJournal of Clinical Oncology
כרך31
מספר גיליון6
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 20 פבר׳ 2013
פורסם באופן חיצוניכן

טביעת אצבע

להלן מוצגים תחומי המחקר של הפרסום 'High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult philadelphia chromosome-negative acute lymphoblastic leukemia'. יחד הם יוצרים טביעת אצבע ייחודית.

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