Marqibo®, Vincristine Sulfate Liposome Injection, for the Treatment of Advanced, Relapsed or Refractory Philadelphia Chromosome-Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) in an Adolescent Young Adult (AYA) Population

Background: Patients aged 15 to 39 years old constitute the Adolescent Young Adult (AYA) population. In the US, leukemias represent ~6% of all cancers in this population with the incidence of Acute Lymphoblastic Leukemia (ALL) gradually decreasing with age as the incidence of acute and chronic myeloid leukemias (AML, CML, respectively) increase; ALL occurs at approximately twice the rate of AML in 15- to 19-year olds. Further studies are needed to define the unique features of leukemia in AYA patients, and to better assess and optimize treatment regimens.

Marqibo®, vincristine sulfate liposome injection, uses a novel sphingomyelin and cholesterol nanoparticle that facilitates vincristine dose intensification without exacerbation of its toxicity, i.e., it has a wider therapeutic index than standard formulation vincristine. This formulation has also been shown to enhance the penetration and concentration of vincristine into tumors, and prolong plasma circulation time in non-clinical experiments.

Marqibo is approved in the US for the treatment of adult patients with Philadelphia chromosome negative (Ph-) ALL in second or greater relapse, whose disease has progressed following two or more previous lines of therapy. We performed a retrospective analysis of data from the Phase 2 RALLY clinical trial (n=65) to examine the effects of Marqibo in the subgroup of the AYA population. The Phase 2 study results of the entire study demonstrated that treatment with single-agent Marqibo resulted in an Overall Response Rate (ORR) of 35%, with 20% of patients achieving a Complete Response (CR) or CR with Incomplete Blood Count Recovery (CRi) (O'Brien, S., 2012 J Clin Oncol).

Methods: Data from the RALLY Phase 2 study of Marqibo were analyzed retrospectively to examine only the relapsed or refractory Ph- ALL patients 39 years of age and younger (n=44). In this study, Marqibo (2.25mg/m²) was administered via IV over 60 minutes without dose capping, once per week until response, progression, toxicity or hematopoietic transplant.

Results: The median age of the 44 patients was 27 (range: 19-39), 57% were male, 82% had B-cell ALL and 18% had T-cell ALL. 84% had ECOG performance status of 0 or 1. The number of previous treatments ranged from 2-6. 41% had 2 prior lines of treatment, 41% had 3 prior lines of treatment, 16% had 4 prior lines of treatment and 2% had 6 prior lines of treatment. In addition, 59% of patients had previously received a hematopoietic cell transplant. The ORR in the AYA population was 39%, with 25% of patients achieving a CR or CRi. Overall, the safety profile of Marqibo was similar to that in the older adult population, with 35 (79.5%) patients having a treatment-related adverse event, of any grade, on study. The most common treatment-related adverse events, of any grade, in the AYA population were constipation (34%) and peripheral neuropathy (32%).

Conclusions: Marqibo (vincristine sulfate liposome injection) was shown to have clinical benefit in AYA patients with relapsed or refractory Ph- ALL with similar safety and efficacy profiles compared to the entire adult population (range: 19-83).