The U.S. Food and Drug Administration (FDA) today approved Besponsa (inotuzumab ozogamicin) in the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) - a rare form of ALL.
Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research in a statement said that in adult patients with B-cell ALL who have failed to respond to initial treatment or have returned after treatment failure, the chances of survival is low and so is the life expectancy. This new treatment could be a targeted treatment that could benefit this group of patients.
The newly approved drug Besponsa binds to the B-cell ALL cancer cells which have a specia marker called the CD22 antigen. Upon binding the drug prevents the cancer cells from growing. For approval the authorities were submitted a trail results that included 326 patients with relapsed or refractory B-cell ALL. This was a randomized trial where patients were randomly divided into two groups –one group received Besponsa and the other received an alternative chemotherapy regimen.
The patients included in the trial had all received one or two prior treatments. Results were assessed by checking on the percentage of patients who made a full recovery from their disease as was evidenced by their blood counts (Complete remission or CR). Results revealed that of the 218 evaluated patients, 35.8 percent who received Besponsa experienced complete remission for a median or average period of 8 months. In the patients of the alternative chemotherapy group the remission rates were 17.4 percent for a median or average of 4.9 months. This difference was statistically and clinical significant enough to warrant treatment with Besponsa in this small group of patients with this rare cancer.
Upon use of Besponsa, the commonly reported side effects include fall in the platelet counts leading to thromobocytopenia and bleeding tendencies, low levels of white blood cells (neutropenia, leukopenia), fall in red blood cell counts, nausea, headache, fatigue, fever, abdominal pain, liver damage etc. the label of the drug would carry a boxed warning too regarding its potential to cause liver damage. The warning also states that the drug could cause blockage of veins in the liver or VOD or sinusoidal obstruction syndrome which could be problematic. Besponsa after receiving a certain type of stem cell transplant could lead to deaths as was seen from the safety trials and this also features in the drug label warning. Women who are pregnant or breastfeeding are not to be prescribed Besponsa because it may harm the developing fetus or the newborn breastfeeding baby.
Besponsa received orphan drug designation that assisted its development and studies and also provided the manufacturers incentives. Orphan drug status is in place to help development of drugs for rare diseases. The FDA granted the approval of making and marketing Besponsa to Pfizer Inc. the drug is already approved in the European Union earlier this year.
B-cell Precursor ALL
B-cell precursor ALL is a fast progressing cancer of the bone marrow in which the bone marrow cells are cancerous and make too many B-cells lymphocytes. These cells are an immature form of white blood cells that flood the blood stream raising the counts. According to the estimates from the National Cancer Institute, ALL will affect about 5,970 people in the United States this year and kill around 1,440.
Some of the common risk factors for ALL include radiation exposure, genetic predisposition, male gender etc. Precursor B-lymphoblastic leukemia symptoms are similar to other forms of acute lymphblastic leukemia – unexplained fever, weight loss, loss of appetite, bleeding gums, pale skin, weakness, vomiting, bruising, lumps or glands swelling around the neck, stomach, underarms etc.
Diagnosis is made using blood tests, bone marrow aspiration and biopsy, cytogenetic analysis and immunophenotyping. Patients with Precursor B-lymphoblastic leukemia are treated with standard chemotherapy. The first part of treatment is called induction therapy and includes several chemotherapy drugs. Once a patient is in remission more chemotherapy is needed to render the patient cancer free for as long as possible.