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 J Maness-Harris, Arnon Nagler, Jacob Rowe, Markus Schaich & 7 others Ofer Shpilberg, Karen Yee, Guenter Schmieder, Jeffrey A. Silverman, Deborah Thomas, Steven R. Deitcher, Hagop Kantarjian

Research output: Contribution to journalArticle

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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

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Philadelphia Chromosome
Vincristine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Liposomes
Injections
Cell Transplantation
Sphingomyelins
Mortality
Nanoparticles
Survivors
Leukemia
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult philadelphia chromosome-negative acute lymphoblastic leukemia. / O'Brien, Susan; Schiller, Gary; Lister, John; Damon, Lloyd; Goldberg, Stuart; Aulitzky, Walter; Ben-Yehuda, Dina; Stock, Wendy; Coutre, Steven; Douer, Dan; Heffner, Leonard T.; Larson, Melissa; Seiter, Karen; Smith, Scott; Assouline, Sarit; Kuriakose, Philip; Maness-Harris, Lori J; Nagler, Arnon; Rowe, Jacob; Schaich, Markus; Shpilberg, Ofer; Yee, Karen; Schmieder, Guenter; Silverman, Jeffrey A.; Thomas, Deborah; Deitcher, Steven R.; Kantarjian, Hagop.

In: Journal of Clinical Oncology, Vol. 31, No. 6, 20.02.2013, p. 676-683.

Research output: Contribution to journalArticle

O'Brien, S, Schiller, G, Lister, J, Damon, L, Goldberg, S, Aulitzky, W, Ben-Yehuda, D, Stock, W, Coutre, S, Douer, D, Heffner, LT, Larson, M, Seiter, K, Smith, S, Assouline, S, Kuriakose, P, Maness-Harris, LJ, Nagler, A, Rowe, J, Schaich, M, Shpilberg, O, Yee, K, Schmieder, G, Silverman, JA, Thomas, D, Deitcher, SR & 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, vol. 31, no. 6, pp. 676-683. https://doi.org/10.1200/JCO.2012.46.2309
O'Brien, Susan ; Schiller, Gary ; Lister, John ; Damon, Lloyd ; Goldberg, Stuart ; Aulitzky, Walter ; Ben-Yehuda, Dina ; Stock, Wendy ; Coutre, Steven ; Douer, Dan ; Heffner, Leonard T. ; Larson, Melissa ; Seiter, Karen ; Smith, Scott ; Assouline, Sarit ; Kuriakose, Philip ; Maness-Harris, Lori J ; Nagler, Arnon ; Rowe, Jacob ; Schaich, Markus ; Shpilberg, Ofer ; Yee, Karen ; Schmieder, Guenter ; Silverman, Jeffrey A. ; Thomas, Deborah ; Deitcher, Steven R. ; Kantarjian, Hagop. / High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult philadelphia chromosome-negative acute lymphoblastic leukemia. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 6. pp. 676-683.
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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.",
author = "Susan O'Brien and Gary Schiller and John Lister and Lloyd Damon and Stuart Goldberg and Walter Aulitzky and Dina Ben-Yehuda and Wendy Stock and Steven Coutre and Dan Douer and Heffner, {Leonard T.} and Melissa Larson and Karen Seiter and Scott Smith and Sarit Assouline and Philip Kuriakose and Maness-Harris, {Lori J} and Arnon Nagler and Jacob Rowe and Markus Schaich and Ofer Shpilberg and Karen Yee and Guenter Schmieder and Silverman, {Jeffrey A.} and Deborah Thomas and Deitcher, {Steven R.} and Hagop Kantarjian",
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T1 - High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult philadelphia chromosome-negative acute lymphoblastic leukemia

AU - O'Brien, Susan

AU - Schiller, Gary

AU - Lister, John

AU - Damon, Lloyd

AU - Goldberg, Stuart

AU - Aulitzky, Walter

AU - Ben-Yehuda, Dina

AU - Stock, Wendy

AU - Coutre, Steven

AU - Douer, Dan

AU - Heffner, Leonard T.

AU - Larson, Melissa

AU - Seiter, Karen

AU - Smith, Scott

AU - Assouline, Sarit

AU - Kuriakose, Philip

AU - Maness-Harris, Lori J

AU - Nagler, Arnon

AU - Rowe, Jacob

AU - Schaich, Markus

AU - Shpilberg, Ofer

AU - Yee, Karen

AU - Schmieder, Guenter

AU - Silverman, Jeffrey A.

AU - Thomas, Deborah

AU - Deitcher, Steven R.

AU - Kantarjian, Hagop

PY - 2013/2/20

Y1 - 2013/2/20

N2 - 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.

AB - 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.

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DO - 10.1200/JCO.2012.46.2309

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EP - 683

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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