Blincyto Prolongs Survival in Acute Lymphoblastic Leukemia (ALL)
by Dr. C.H. Weaver M.D. updated 12/2020
Blincyto (blinatumomab) induces high complete remission rates and prolongs survival in patients with relapsed/refractory B-precursor acute lymphoblastic lymphoma (ALL) and both Philadelphia positive and negative ALL.
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.
About Blincyto (blinatumomab)
Blincyto is a 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. Blincyto is the first of the BiTE® antibody construct approved by the US Food and Drug Administration and its incorporation into the management of ALL is improving patient outcomes.
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.
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% of patients achieved a hematological complete response (CR) or CR with partial hematological recovery (CRh) and 10 out of 36 (28%) achieved CRh following Blincyto treatment. Doctors have since been evaluating how best to incorporate Blincyto into the overall management of ALL.
Blincyto Should be Added to Chemotherapy Consolidation in ALL
Study findings presented at the 62nd American Society of Hematology (ASH) Annual Meeting in December 2020 suggest that Blincyto monotherapy should be considered a new standard-of-care consolidation therapy used before allogeneic hematopoietic stem cell transplant (alloHSCT) in young patients with high risk first relapse B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Between November 2015 and to July 2019 108 patients with BCP-ALL were enrolled in a clinical trial designed to compare Blincyto to chemotherapy pre-transplant consolidation therapy for children with high-risk first relapse BCP-ALL.
All patients were treated with induction chemotherapy and 2 cycles of consolidation chemotherapy; half the patients then received either a third cycle of consolidation chemotherapy or Blincyto daily for 4 weeks before proceeding to alloHSCT.
Blincyto was shown to improve survival and reduce the risk for relapse by 64% compared with chemotherapy. A minimal state residual leukemia was attained in 93% of Blincyto treated patients compared to 54% of those treated with chemotherapy.
The study authors concluded that “Blincyto monotherapy as consolidation therapy before alloHSCT in children with high-risk first-relapse BCP-ALL leads to significantly better outcomes including a lower risk of recurrence, and significant side effects than chemotherapuy suggesting a new standard‑of-care
Blincyto® Improves Survival in Advanced 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 Blincyto 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 Blincyto salvage, with or without a tyrosine kinase inhibitor, following CAR-T cell therapy or consolidation are warranted.
Blincyto Side Effects: The most side effects reported with Blincyto include were fever, headache, peripheral edema, febrile neutropenia, nausea, low potassium, rash, tremor, and constipation. Neurological toxicity occurred in approximately 50% of patients and was a frequent reason for interruption of therapy in early trials. Cytokine release syndrome has beeen reported in 10-20% of patients including both life-threatening and fatal events.
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- 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.
- Locatelli F, Zugmaier G, Rizzari C, et al. Superior Event-Free Survival with Blincyto Versus Chemotherapy in Children with High-Risk First Relapse of B-Cell Precursor Acute Lymphoblastic Leukemia: A Randomized, Controlled Phase 3 Trial. Presented at: the 62nd ASH Annual Meeting and Exposition; December 5-8, 2020; virtual. Abstract 268.