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tisagenlecleucel (Kymria)

Indications: - hematopoietic malignancies - refractory acute lymphoblastic leukemia* * B-cell precursor acute lymphoblastic leukemia (FDA-approved 8/2017) Procedure: - a tumor-binding element is introduced into a patient's T-cells using viral vectors - these T-cells are cultured to produce large numbers of such cells, then reinfused into the patient - modified T-cells attack leukemia cells with CD19 antigen (B-cells) Monitor: - neurologic assessment every 8 hours Adverse effects: - cytokine release syndrome (cytokine storm)* most common - CAR T-cell-related encephalopathy (CRES) 2nd most common - may result in fatal cerebral edema [4] * boxed warning Laboratory: - daily starting day of infusion - complete blood count QD - chemistry 14 panel - PT, aPTT, INR - serum C-reactive protein - serum ferritin Clinical trials: - pediatric & young adult patients with relapsed or refractory B-cell ALL - a single infusion of tisagenlecleucel - durable remission with long-term persistence in - transient high-grade toxic effects [7] Notes: - list price is $475,000 for one-time treatment [3]

General

chimeric antigen-receptor (CAR) T-cell therapy; tisagenlecleucel; CTL019 (Kymriah) antineoplastic agent (chemotherapeutic agent)

References

  1. Komaroff AL Immunotherapy to Fight Cancer Begins to Work. NEJM Journal Watch. June 16, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
  2. Gever J FDA Approves CAR T-Cell Therapy for Leukemia. 'First gene therapy available in the United States,' says agency. MedPage Today. August 30, 2017 https://www.medpagetoday.com/HematologyOncology/Leukemia/67615 - FDA News Release. Aug 30, 2017 FDA approval brings first gene therapy to the United States. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm - Windle ML. FDA New Drug and Biologic Approvals -- 2017 Year-in-Review Medscape - Jan 11, 2018. https://reference.medscape.com/viewarticle/890871 - U.S. Food and Drug Administration. Novel Drug Approvals for 2017. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm537040.htm
  3. Court E Novartis' CAR-T gene therapy, the first approved by FDA, to cost $475,000 MarketWatch. Aug 31, 2017 http://www.marketwatch.com/story/novartis-car-t-gene-therapy-the-first-approved-by-fda-to-be-priced-based-on-cancer-patients-outcomes-2017-08-30
  4. Anello J, Feinberg B, Heinegg J et. al. New Guidelines and Recommendations, October 2017 Medscape - Oct 06, 2017 http://reference.medscape.com/viewarticle/886616_5
  5. Bach PB, Giralt SA, Saltz LB. FDA Approval of TisagenlecleucelPromise and Complexities of a $475,000 Cancer Drug. JAMA. 2017;318(19):1861-1862 PMID: 28975266 https://jamanetwork.com/journals/jama/article-abstract/2654900
  6. Buechner J, et al. Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL): Update to the interim analysis European Hematology Association Annual Meeting. June 24, 2017;Abstract S476.
  7. Maude SL, Laetsch TW, Buechner J et al Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med 2018; 378:439-448. Feb 1, 2018 PMID: 29385370 http://www.nejm.org/doi/full/10.1056/NEJMoa1709866