title: High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia.
abstract: OBJECTIVE
  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).
  
  
  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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Texas, MD Anderson Cancer Center, Houston, TX, USA
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Gary
authors.initials: G
authors.lastname: Schiller
authors.forename: John
authors.initials: J
authors.lastname: Lister
authors.forename: Lloyd
authors.initials: L
authors.lastname: Damon
authors.forename: Stuart
authors.initials: S
authors.lastname: Goldberg
authors.forename: Walter
authors.initials: W
authors.lastname: Aulitzky
authors.forename: Dina
authors.initials: D
authors.lastname: Ben-Yehuda
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.forename: Steven
authors.initials: S
authors.lastname: Coutre
authors.forename: Dan
authors.initials: D
authors.lastname: Douer
authors.forename: Leonard T
authors.initials: LT
authors.lastname: Heffner
authors.forename: Melissa
authors.initials: M
authors.lastname: Larson
authors.forename: Karen
authors.initials: K
authors.lastname: Seiter
authors.forename: Scott
authors.initials: S
authors.lastname: Smith
authors.forename: Sarit
authors.initials: S
authors.lastname: Assouline
authors.forename: Philip
authors.initials: P
authors.lastname: Kuriakose
authors.forename: Lori
authors.initials: L
authors.lastname: Maness
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Jacob
authors.initials: J
authors.lastname: Rowe
authors.forename: Markus
authors.initials: M
authors.lastname: Schaich
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Karen
authors.initials: K
authors.lastname: Yee
authors.forename: Guenter
authors.initials: G
authors.lastname: Schmieder
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Silverman
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Steven R
authors.initials: SR
authors.lastname: Deitcher
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014750:Vincristine