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Amgen Presents Data From Three Trials Evaluating BLINCYTO® (blinatumomab) In Acute Lymphoblastic Leukemia At ASH 2015
In a Phase 2 confirmatory multicenter single-arm trial (BLAST), adult patients with B-cell precursor ALL with minimal residual disease (MRD) who received BLINCYTO monotherapy demonstrated clinically meaningful relapse-free survival (RFS), as measured in the key secondary endpoint (abstract #680). Median RFS was 18.9 months following initiation of BLINCYTO. MRD refers to the presence of leukemia blast cells below the limits of detection available with standard assessment. Results from the Phase 2 BLAST trial were nominated for inclusion in the Best of ASH Session on
Other presentations demonstrate BLINCYTO's potential in a high risk subpopulation of patients with relapsed or refractory
"A key goal in the treatment of blood cancers is to prevent relapse from occurring," said
ALL is a rare and rapidly progressing cancer of the blood and bone marrow.1,2 In adult patients with relapsed or refractory ALL, median overall survival (OS) is just three to five months.3 Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy.4 Around 15-30 percent of adult ALL patients are Ph+ and these patients typically have a poor response to standard therapy, short remission duration and low survival rates.5
Abstracts are currently available on the ASH website.
ASH Abstract #680: Long-Term Outcomes After Blinatumomab Treatment: Follow-up of a Phase 2 Study in Patients With Minimal Residual Disease (MRD) Positive B-cell Precursor ALL
- In this long-term follow up from the Phase 2 '203 study of 116 patients with B-precursor ALL and persistent or recurrent MRD after first-line chemotherapy, patients who achieved an MRD complete response with BLINCYTO had a longer OS, RFS and duration of remission (DOR) compared with those not achieving an MRD complete response, with a median OS in MRD-negative patients of 40.4 months. In data reported at ASH 2014, treatment with BLINCYTO resulted in complete MRD response in cycle 1 in 78 percent of patients.
- The most clinically relevant adverse events (AEs) were neurologic events, including tremor (30 percent), aphasia (13 percent), dizziness (8 percent), ataxia and paresthesia (6 percent each), and encephalopathy (5 percent). Rates decreased over time (cycles 1, 2, 3 and 4) for any neurologic event (47 percent, 24 percent, 15 percent and 15 percent) and any grade 3 or higher neurologic event (10 percent, 4 percent, 0 percent and 0 percent).
ASH Abstract #679: Complete Molecular and Hematologic Response in Adult Patients with Relapsed/Refractory (R/R) Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia (ALL) Following Treatment with Blinatumomab: Results from a Phase 2 Single-Arm, Multicenter Study (ALCANTARA)
- In the Phase 2 ALCANTARA study, BLINCYTO showed antileukemic activity in very poor prognosis patients with relapsed or refractory Ph+ B-precursor ALL after failure of at least one second-generation tyrosine kinase inhibitor (TKI) therapy, with 36 percent of patients achieving complete remission or complete remission with partial hematological recovery (CR/CRh) during the first two treatment cycles. Of patients who achieved CR/CRh, 88 percent achieved a complete MRD response. Equivalent response rates were observed in patients with kinase-domain mutations in BCR-ABL such as T315I (four achieved CR/CRh; all four also achieved a complete MRD response).
- Patient incidence of grade 3 or higher treatment-emergent AEs was 82 percent, most commonly febrile neutropenia (27 percent), thrombocytopenia (22 percent), anemia (16 percent), pyrexia (11 percent) and neurologic events (7 percent). There were no episodes of grade 3 or higher cytokine release syndrome.
ASH Abstract #861: Treatment with anti-CD19 BiTE® Blinatumomab in Adult Patients with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) Post-Allogeneic Hematopoietic Stem Cell Transplantation
- In this analysis from the pivotal Phase 2 '211 trial, BLINCYTO induced a CR/CRh rate of 45 percent in a subset of 64 heavily pretreated patients with Ph- ALL who had relapsed or were refractory after an alloHSCT.
- In total, 88 percent of patients had grade 3 or higher treatment-emergent AEs, with the most frequent including neutropenia (22 percent), febrile neutropenia (20 percent), anemia (17 percent) and thrombocytopenia (14 percent). Six patients reported treatment-emergent graft vs. host disease (GvHD), two of which were grade 3 or higher.
Amgen Webcast Investor Meeting
Live audio of the conference call will be simultaneously broadcast over the Internet and will be available to members of the news media, investors and the general public.
The webcast, as with other selected presentations regarding developments in
About BLINCYTO® (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. BLINCYTO was granted breakthrough therapy and priority review designations by the
About BiTE® Technology
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.
BLINCYTO® U.S. Product Safety Information
Important Safety Information Regarding BLINCYTO® (blinatumomab) U.S. Indication
This safety information is specific to the current U.S. approved indication.
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
- Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
- Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Warnings and Precautions
Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO®. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO® as outlined in the Prescribing Information (PI).
Neurological Toxicities: Approximately 50% of patients receiving BLINCYTO® in clinical trials experienced neurological toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO® as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO® experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed.
Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment. The majority of these events were observed in the setting of CRS. The median time to onset was 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and anti-leukemic chemotherapy. Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
The most commonly reported adverse reactions (≥ 20%) in clinical trials were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), diarrhea (20%) and constipation (20%).
Serious adverse reactions were reported in 65% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, pneumonia, sepsis, neutropenia, device-related infection, tremor, encephalopathy, infection, overdose, confusion, Staphylococcal bacteremia, and headache.
U.S. Dosage and Administration Guidelines
BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm. It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full U.S. Prescribing Information and medication guide for BLINCYTO® at www.BLINCYTO.com.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist.
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The scientific information discussed in this news release relating to new indications for
Cancer Research UK. Acute lymphoblastic leukaemia risks and causes. _http://www.cancerresearchuk.org/about-cancer/type/all/about/acute-lymphoblastic-leukaemia-risks-and-causes. Accessed September 29, 2015. Mayo Clinic. "Acute lymphocytic leukemia." Available at: _http://www.mayoclinic.com/health/acute-lymphocytic-leukemia/DS00558. Accessed on March 5, 2015. Advani A.S. Newimmune strategies for the treatment of acute lymphoblastic leukemia: Antibodies and chimeric antigen receptors. Hematology Am Soc Hematol Educ Program. 2013;2013:131-7. Retrieved from: _http://asheducationbook.hematologylibrary.org/content/2013/1/131.long.
- Davis T and Farag SS. Treating relapsed or refractory
Philadelphiachromosome-negative acute lymphoblastic leukemia: liposome-encapsulated vincristine. Int J Nanomedicine. 2013:8 3479-3488.
- Faderl S et al. Outcome of
Philadelphiachromosome-positive adult lymphoblastic leukemia. Leukemia and Lymphoma. 2000;36(3-4):263-273.
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