Blinatumomab Prolongs Survival in Relapsed/Refractory Adult ALL

Posted on December 14th, 2012 by

Blinatumomab induces high complete remission rates and prolongs survival in adult patients with relapsed/refractory B-precursor acute lymphoblastic lymphoma (ALL), according to the results of a study presented at the 54th Annual Meeting of the American Society of Hematology in Atlanta, Georgia.

Acute lymphoblastic lymphoma (ALL) is a fast-growing cancer of the white blood cells. Relapsed/refractory B-precursor ALL in adults has a dismal prognosis, with only 35–40 percent of patients reaching a hematological complete remission (CR) and a median overall survival of 4–6 months.

Blinatumomab is a bispecific T cell engager (BiTE®) antibody. BiTE antibodies are designed to engage two different targets simultaneously. This dual binding ability allows BiTE antibodies to act as bridges between T cells (a type of white blood cell capable of killing other cells perceived as threats) and tumor cells. Blinatumomab is designed to direct the T cells to target cells expressing CD19, a protein found on the surface of most B cell derived leukemias and lymphomas. Blinatumomab has received orphan drug designation from the U.S. Food and Drug Administration (FDA) and is currently being investigated for the treatment of ALL and non-Hodgkin’s lymphoma.

Researchers conducted an exploratory phase II study to evaluate blinatumomab in 36 adult patients with relapsed/refractory B-precursor ALL. Patients received a continuous intravenous infusion of blinatumomab for 28 days followed by a 14-day treatment-free interval. Patients who experienced a response had the option to receive 3 additional cycles of treatment or proceed to allogeneic stem cell transplantation.

The results indicated that 26 out of 36 patients (72%) achieved a hematological complete response (CR) or CR with partial hematological recovery (CRh) and 10 out of 26 (38%) achieved CRh. In addition, 24 out 26 (92%) responders achieved a molecular response (minimal residual disease level below 10–4 as measured by PCR) within the first 2 cycles. Twenty out of 21 (95%) patients in first relapse responded, whereas only 6 out of 15 (40%) of the remaining patients achieved a hematological CR/CRh*. Thirteen patients proceeded to allogeneic HSCT in CR/CRh after blinatumomab treatment.

The median survival for all 36 treated patients is 9.0 months with a median follow-up time for overall survival of 10.7 months. Median survival for patients who achieved a CR/CRh is 14.1 months, compared to 6.6 months for patients who failed blinatumomab therapy.

Adverse events were generally acceptable, with the most common adverse events being fever, headache, tremor, and fatigue. Some patients experienced cytokine release syndrome (CRS) and central nervous system events, including seizures and encephalopathy. One patient stopped treatment due to fungal infection leading to death.

The researchers concluded that blinatumomab was well-tolerated and produced exceptionally high complete hematological and molecular remission rates. Research is ongoing to confirm these results.

Reference:

Topp MS, Goekbuget N, Zugmaier G, et al. Anti-CD19 BiTE blinatumomab induces high complete remission rate and prolongs overall survival in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). Blood (ASH Annual Meeting Abstracts) 2012; 120: Abstract 670.

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Tags: Acute Lymphoblastic Leukemia, Leukemia, News

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