by Dr. C.H. Weaver M.D. updated 3/2019
Blincyto (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.
Blincyto 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. Blincyto 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.
Researchers conducted an exploratory phase II study to evaluate Blincyto in 36 adult patients with relapsed/refractory B-precursor ALL. Patients received a continuous intravenous infusion of Blincyto 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 69 percent of patients achieved a hematological complete response (CR) or CR with partial hematological recovery (CRh) and 10 out of 36 (28%) achieved CRh. In addition, 88 percent (22/25 responders) of patients achieved a molecular response (minimal residual disease level below 10–4 as measured by PCR) within the first 2 cycles. Median relapse-free survival in the 25 patients who responded to treatment was 7.6 months. 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 9.8 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.
Blincyto-Ponatinib Salvage Therapy in B-Cell Acute Lymphoblastic Leukemia: Case Report of Benefit
Doctors have reported that a 42-year old man with heavily-pretreated relapsed Philadelphia chromosome-positive, CD19-positive, pre-B ALL who was previously treated with CD19 chimeric antigen receptor-T (CAR-T) cell therapy experienced a complete response (CR) for 12 months following subsequent combination therapy with Blincyto and ponatinib.(2)
Upon disease relapse following CAR-T cell therapy, the patient received 4 courses of combination therapy with standard-dose blinatumomab and the tyrosine kinase inhibitor, ponatinib (30 mg daily), followed by ponatinib maintenance therapy. The patient achieved molecular remission and a CR lasting 12 months.
This is the first report of pre-B-ALL responding to CD19/CD3 BiTE therapy in combination with a tyrosine kinase inhibitor after failure of CD19 CAR-T therapy,” the study authors wrote.
Further studies exploring the role of blinatumomab salvage, with or without a tyrosine kinase inhibitor, following CAR-T cell therapy or consolidation are warranted.
- El Chaer F, Holtzman NG, Sausville EA, et al. Relapsed Philadelphia Chromosome-positive pre-B-ALL after CD19-directed CAR-T cell therapy successfully treated with combination of blinatumomab and ponatinib. Acta Haematol. 2019;141(2):107-110.
- 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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