Rare Disease Report

Data for Two Newly Approved Drugs for Rare Hematologic Malignancies at ASH

FEBRUARY 28, 2015
Christin L. Melton, ELS

The US Food and Drug Administration (FDA) issued two new drug approvals for hematologic malignancies just ahead of the 56th ASH Annual Meeting & Exposition.

The FDA awarded accelerated approval to the immunotherapy drug Blincyto (blinatumomab) to treat relapsed or refractory precursor B-cell acute lymphoblastic leukemia (B-cell ALL) in patients who are Philadelphia chromosome–negative. B-cell ALL is a form of ALL, a rapidly progressing hematologic cancer. Blincyto is a bi-specific T-cell engaging antibody, also known as a BiTE antibody, administered as a continuous intravenous infusion. In the bloodstream, the drug targets CD19, an antigen typically found on the surface of malignant B cells in patients with B-cell ALL. Blincyto also binds to CD3, present on the surface of T cells. As Blincyto links the cytotoxic T cell with the malignant B cell, the T cell begins releasing inflammatory cytokines and a proliferation of T cells until the bound B cell is destroyed. This leaves the activated T cell free to target and kill additional malignant cells.

In the study that led to FDA-approval of Blincyto, 32% of the 185 enrolled adults with B-cell ALL who received the drug for at least 4 weeks experienced complete remission for approximately 6.7 months. (For more on the pivotal study that led to Blincyto’s approval, click here). The FDA is requiring a black box warning and a Risk Evaluation and Mitigation Strategy for Blincyto, which caused low blood pressure and breathing problems in some patients after their first infusion. Others experienced adverse central nervous system effects.

Several studies on Blincyto in adults and children with precursor B-cell ALL are being presented at ASH. Nicola Goekbuget, MD, from Goethe University Hospital, Frankfurt, Germany, is giving an oral presentation on findings from the phase 2 BLAST trial, which enrolled 116 adults with minimal residual disease (Abstract 379). Gerhard Zugmaier, MD, from Amgen Research, Munich, Germany, is presenting a poster on long-term survival outcomes for 36 adults treated with up to 5 cycles of Blincyto (Abstract 2287).  Lia Gore, MD, from Children’s Hospital Colorado, Aurora, CO, is presenting a poster that includes the initial findings from a phase 2 study of Blincyto in 39 children aged 2 to 16 years (Abstract 3703).

The FDA also approved Jakafi (ruxolitinib) (which the FDA approved in 2011 to treat intermediate- or high-risk myelofibrosis), for polycythemia vera (PV) in patients unable to tolerate or resistant to hydroxyurea. According to the Leukemia & Lymphoma Society, PV is a myeloproliferative neoplasm in which the bone marrow overproduces red blood cells, and its estimated prevalence is 22 cases per 100,000 people. Approximately 95% of patients with this rare incurable disorder have a Janus kinase 2 (JAK2) gene mutation, thought to play a role in PV development. Jakafi is a small-molecule agent that selectively targets and inhibits JAK1 and JAK2, reducing the risk of PV-related splenomegaly. In the pivotal phase 3 RESPONSE trial involving 222 patients with PV randomly assigned to Jakafi (10 mg twice daily) or standard care, 21% of patients in the Jakafi arm versus 1% of patients in the standard care arm had a reduction in spleen volume and a reduced need for phlebotomy.

At the ASH meeting, Ruben Mesa, MD, from Mayo Clinic Cancer Center, Scottsdale, AZ, delivered oral presentations on findings from RELIEF and RESPONSE, two phase 3 trials of Jakafi in patients with PV (Abstracts 3168 and 709).

In addition, Srdan Verstovsek, MD, from the Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, and Alessandro M. Vannucchi, MD, from the University of Florence, Florence, Italy, are presenting separate subanalyses from the RESPONSE trial during oral sessions (Abstracts 3201 and 1840, respectively).

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