High-dose monotherapy with vincristine sulfate liposome injection (Marqibo) resulted in meaningful clinical outcomes, including durable responses and bridging to hematopoietic cell transplantation, in adult patients with advanced, relapsed, and refractory Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL), according to a study reported in the Journal of Clinical Oncology. This “near end-stage adult ALL population” is “desperately in need of new therapies,” the authors noted.
Liposomal vincristine is a nanoparticle formulation of vincristine “designed to overcome the dosing and pharmacokinetic limitations of standard, nonliposomal vincristine,” the authors explained. “This study,” they noted, “served as the basis for accelerated approval” of liposomal vincristine in the United States.
The phase II multinational study involved 65 patients with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies. “Intravenous [liposomal vincristine] 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of [hematopoietic cell transplantation],” the researchers stated.
The overall response rate was 35%, and the rate of complete response or complete response with incomplete hematologic recovery was 20%, with a median complete response duration of 23 weeks (range, 5–66 weeks). “Younger age and higher baseline platelet count were independently associated with a favorable response,” the investigators noted.
“[Liposomal vincristine] monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies,” the researchers wrote. Twelve patients (19%) bridged to hematopoietic cell transplantation. Median overall survival was 4.6 months and 7.7 months in those achieving complete response or complete response with incomplete hematologic recovery. Five patients survived for more than 1 year.
“The toxicity profile of [liposomal vincristine] was predictable, manageable, and comparable to standard [vincristine] despite the delivery of large, normally unachievable, individual and cumulative doses of [vincristine],” the investigators stated. [Liposomal vincristine] was “associated with a low 30-day mortality rate (12%).”
Based on this study and other phase II studies successfully combining [liposomal vincristine] with other chemotherapies and rituximab (Rituxan), patients with front-line adult ALL and front-line aggressive non-Hodgkin lymphoma are being enrolled in phase III studies. ■
O’Brien S, et al: J Clin Oncol 31:676-683, 2013.