Blincyto Prolongs Survival in Relapsed/Refractory Adult ALL
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) and both Philadelphia positive and negative ALL.
About Blincyto (blinatumomab)
Blincytois an investigational BiTE® antibody construct designed to direct the body’s cell-destroying T cells against target cells expressing CD19, a protein found on the surface of B-cell derived leukemias and lymphomas. Blinatumomab is the first of the BiTE® antibody constructs.
About BiTE® Technology Bispecific T cell engager (BiTE®) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE® antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.
Acute lymphoblastic leukemia is an aggressive cancer of the blood and bone marrow, the spongy tissue inside bones where blood cells are made.1 The disease progresses rapidly and affects immature blood cells. Worldwide, ALL accounts for more than 12 percent of leukemia. Of the 42,000 people diagnosed worldwide, 31,000 will die from the disease. Patients with ALL have abnormal white blood cells (lymphocytes) that crowd out healthy white blood cells, red blood cells and platelets, leading to infection, anemia (fatigue), easy bleeding and other serious side effects.
Safety has been reported in 212 patients who treated with Blincyto. The most common adverse reactions were fever (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), low potassium (23%), rash (21%), tremor (20%), and constipation (20%). Neurological toxicity occurred in approximately 50% of patients and was a frequent reason for interruption of therapy. Cytokine release syndrome was reported in 11% of the patients including both life-threatening and fatal events.
The initial exploratory study to evaluate Blincyto was 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. Overall 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.
Blincyto® Improves Survival in Philadelphia chromosome-negative (Ph-) ALL
Blincyto improves survival compared to standard therapy among patients with B-cell precursor, Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (BCP-ALL) that has stopped responding to prior therapies. Results presented at the 2016 EHA meeting were updated from the TOWER trial, which included 405 patients with B-cell precursor, Ph-, ALL. All patients had progression of their cancer despite prior therapies. In the trial, one group of patients was treated with Blincyto and the other group was treated with standard chemotherapy regimens.
- Median overall survival was 7.8 months for patients treated with Blincyto compared with only 4 months for those treated with standard therapies and anti-cancer responses were significantly higher among the group of patients treated with Blincyto.
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.
- 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.
- Topo M, Stein A, Gokbuget N, et al. Blinatumomab improved overall survival in patients with relapsed or refractory Philadelphia negative B-cell precursor acute lymphoblastic leukemia in a randomized, open-label phase 3 study (TOWER). Proceedings from the 2016 annual EHA meeting. Abstract S149. Available at: . Accessed June 17, 2016.
- Amgen Announces Positive BLINCYTO® (blinatumomab) Phase 2 Study Results In Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Cell Precursor Acute Lymphoblastic Leukemia [press release]. Amgen website. Available at: . Accessed July 20, 2015.
- 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.