Besponsa for B-cell Acute Lymphoblastic Leukemia
Besponsa (inotuzumab ozogamicin) a precision medicine designed to bind to B-cell acute lymphoblastic leukemia (ALL) cancer cells that express the CD22 antigen has been approved by the US FDA and can be used to increase the number of individuals with relapsed refractory ALL attaining complete remission prior to allogeneic stem cell transplant (alloSCT) treatment.
About Acute lymphoblastic leukemia (ALL)
Acute lymphoblastic leukemia - a fast-growing cancer of the white blood cells—is the most commonly diagnosed type of leukemia in children. Each year, there are approximately 4,000 children diagnosed in the United States. The majority of children and a significant fraction of adult patients with ALL can be cured with intensive chemotherapy.1-4 However, many patients relapse and most of these ultimately develop disease that is refractory (resistant) to therapy. Patients with relapsed ALL who respond to chemotherapy are candidates for alloSCT, but good results are not achieved in patients with refractory disease. Thus, there is intensive research to develop novel therapies for the treatment of patients with relapsed and refractory ALL to increase the proportion of patients in remission that can ultimately benefit from treatment with alloSCT.
About Besponsa (Inotuzumab ozogamicin)
Besponsa is a drug that is referred to as an antibody drug conjugate. It is comprised of an antibody that has been developed to specifically bind to the CD22 antigen, which is a small molecule found on the surface of B-cells. Attached to the antibody is a chemotherapy agent called calicheamicin. Once the agent is bound to the B-cell, it is internalized into the cell where the chemotherapy is released into the cell.
The FDA approval of Besponsa came following results of a trial that tested its safety and effectiveness in 326 patients with relapsed or refractory ALL who had received no more than two prior treatments. Patients treated with Besponsa were twice as likely to achieve a complete remission than those treated with standard chemotherapy.5
Immunotherapy After Chemoradiotherapy Promising in Limited-Stage Small Cell Lung Cancer
Adjuvant therapy with Imfinzi (durvalumab) significantly improved survival outcomes for patients with limited-stage SCLC
Breakthrough in Understanding Tamoxifen's Effectiveness in Breast Cancer: Gut Bacteria Play a Crucial Role
Since tamoxifen is taken orally and travels through the digestive system, variations in patient responses may be connected to the gut microbiome—the trillions of bacteria in our intestines that differ significantly from one person to another.
New FDA Approved Treatment Option for HER2-Positive Biliary Tract Cancer
Bispecific HER2-directed antibody now available for unresectable or metastatic HER2-positive BTC
Besponsa significantly delays leukemia recurrence and improves 2-year survival rates among patients with ALL that has stopped responding to prior therapy according to a pivotal study published in the New England Journal of Medicine.
Researchers conducted a clinical trial to evaluate Besponsa among patients with ALL that had progressed, or stopped responding to, prior therapy. The trial, referred to as the INO-VATE ALL Trial, or the Study 1022, was a phase III study that included 326 adults with B-cell ALL that had progressed following prior therapy. The leukemia cells tested positive for the CD22 antigen. Patients were treated with either Besponsa or standard treatment.6
- The median survival time without cancer progression was 5.0 months for patients treated with Besponsa compared with only 1.8 months for those treated with standard therapy.
- Survival at 2 years was 23% for patients treated with Besponsa compared with 10% for those treated with standard therapy.
- 41% of patients treated with Besponsa went on to receive a stem cell transplant, compared with only 11% of patients treated with standard therapy.
- Veno-occlusive disease is the most serious side effect associated with Besponsa.
The researchers concluded that treatment with Besponsa appears superior to standard therapy for treatment of relapsed ALL and may provide an important new treatment option for patients with this disease.
Side effects associated with Besponsa include thrombocytopenia, neutropenia, leukopenia, infection, anemia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, liver damage, abdominal pain, and hyperbilirubinemia.
References:
- FDA approves inotuzumab ozogamicin for relapsed or refractory B-cell precursor ALL
- Oudot, C. Auclerc, F.., Levy, V., et al. Prognostic Factors for Leukemia Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study. Journal of Clinical Oncology, March 2008; Volume 28 (9).
- Chessels, J., Veys, P., Kempski, H., et al. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. British Journal of Hematology, 2003; 123 (3).
- Reismuller, B., Peters, C., Dworzak, M., et al. Outcome of children and adolescents with a second or third relapse of acute lymphoblastic leukemia (ALL): a population-based analysis of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Study Group. Journal of Pediatric Hematology/Oncology. July 2013; 35 (5).
- Jabbour, S. M. O’Brien, D. A. Thomas et al. Inotuzumab ozogamicin (IO; CMC544), a CD22 monoclonal antibody attached to calicheamycin, produces complete response plus complete marrow response (mCR) of greater that 50% in refractory relapse (R-R) acute lymphoblastic leukemia. Journal of Clinical Oncology 29:2011 (supplement, abstract 6507).
- Kantarjian H, DeAngelo D, Steljies M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. New England Journal of Medicine. 2016; 375:740-753. DOI: 10.1056/NEJMoa1509277. Available at: . Accessed August 29, 2016.
