Tisagenlecleucel is a therapy that uses genetically modified T-cells from individual patients with acute lymphoblastic leukemia (ALL).
The FDA granted regular approval to tisagenlecleucel (Kymriah, Novartis) for the treatment of ALL that is refractory or in relapse in patients up to age 25.1 Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell immunotherapy agent. It is the first FDA-approved gene therapy, opening a new era in the treatment of cancer and other life-threatening diseases.
Approval was based on a single-arm trial of 63 pediatric patients with precursor B-cell ALL.3 Patients received a single dose of tisagenlecleucel intravenously within 2 to 14 days following completion of lymphodepleting chemotherapy (fludarabine and cyclophosphamide). The confirmed overall remission rate at 3 months was 82.5% (95% confidence interval [CI], 70.9- 91.0), which is significantly higher than the alternatives.
The most common side effects include: cytokine-release syndrome (CRS) (79%), hypogammaglobulinemia (43%), infections (41%), pyrexia (40%), decreased appetite (37%), headache (37%), encephalopathy (34%), hypotension (31%), and bleeding disorders (31%). Grade 3 or 4 adverse events were reported in 84% of patients.2
Serious side effects include CRS.2 Tisagenlecleucel should not be used in patients with active infections or inflammatory disorders.
During infusion, monitor for hypersensitivity reactions.2 Following therapy, monitor immunoglobulin levels. Avoid administration of live vaccines for 2 weeks before lymphodepleting therapy and, until immune recovery after tisagenlecleucel, monitor for signs and symptoms of infections. Signs and symptoms of CRS including chills, hypotension, tachycardia, rash, scratchy throat, and dyspnea, should also be monitored for at least 4 weeks after infusion. Severe or life-threatening CRS is treated with tocilizumab and/or corticosteroids. The patient should be monitored for neurological events.
Dosing, Availability, Cost
Tisagenlecleucel is only available through certified hospitals and associated clinics.
It is prepared via a standard leukapheresis procedure.2 Cells are then shipped to the manufacturer for processing and shipped back to the treatment center as a frozen suspension labeled for the specific patient. After verifying patient’s identity, the patient should be premedicated with acetaminophen and an H1-antihistamine 30 to 60 minutes before infusion. After the medication is thawed it should be administered within 30 minutes and at a rate of 10 to 20 mL/min.
The recommended dose for tisagenlecleucel in patients weighing 50 kg or less leukapheresis, is 0.2 to 5 x106 CAR-positive viable T cells per kg.2 In patients weighing more than 50 kg at the time of leukapheresis, administer 0.1 to 2.5 x 108 CAR-positive viable T cells (this dose is not weight based). The Certificate of Analysis shipped with the product will list the actual number of CAR-positive T-cells.
The cost of tisagenlecleucel is $475,000 for a single infusion.
1. U.S. Food and Drug Administration. FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome. Available at http://bit.ly/2lzQjMX. Accessed on Oct. 17, 2017.
2. U.S. Food and Drug Administration. FDA Briefing Document: Oncologic Drugs Advisory Committee Meeting. Available at http://bit.ly/2vtaVGM. Accessed on Oct. 17, 2017.
3. Kymriah [Package Insert]. East Hanover, NJ: Novartis Pharmaceuticals. Available at http://bit.ly/2vtaVGM. Accessed on Oct. 17, 2017.
4. U.S. Food and Drug Administration. FDA Briefing Document: Risk Evaluation and Mitigation Strategy. Available at http://bit.ly/2ijhAOE. Accessed on Oct. 17, 2017.