What is the role of tisagenlecleucel (Kymriah) in chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia (ALL)?

Updated: May 04, 2018
  • Author: Sameh Gaballa, MD, MS; Chief Editor: Emmanuel C Besa, MD  more...
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The anti-CD19 agent tisagenlecleucel (Kymriah) is the first CAR T-cell therapy to enter clinical practice. In August 2017, the US Food and Drug Administration (FDA) approved tisagenlecleucel for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse. [8]

Approval of tisagenlecleucel was based on the results of an open-label, multicenter single-arm trial (Study B2202). Eighty-eight children and young adults were enrolled, 68 were treated, and 63 were evaluable for efficacy. Of the 63 evaluable patients, 52 responded, including 40 patients (63%) with a CR within 3 months after infusion, and 12 (19%) with a CR but with incomplete blood count recovery. Bone marrow from all patients demonstrated minimum residual disease–negative status  [9] .

The major toxicity associated with this approach is severe and potentially life-threatening cytokine release syndrome (CRS), discussed in more detail below. In clinical trials, 69% of patients with CRS related to CAR T-cell therapy had complete resolution of CRS within 2 weeks after receiving one or two doses of the anti-IL-6 monoclonal antibody tocilizumab (Actemra). [8]

In conjunction with the approval of tisagenlecleucel, the FDA also expanded the approval of tocilizumab to include the treatment of severe or life-threatening CRS resulting from CAR T-cell therapy in patients 2 years of age or older. Because of the potential for life-threatening adverse effects, the FDA approval mandates inclusion of a risk evaluation and mitigation strategy that requires special certification for hospitals and clinics as well as additional training for physicians and support staff. [8]

As with many new therapies, cost can be a significant barrier to widespread adoption, and the cost of tisagenlecleucel has been estimated at $475,000. However, Novartis, the company that makes tisagenlecleucel, is adopting an outcomes-based approach to pricing, so that the company would be reimbursed only if the patient’s condition responds by the end of the first month of treatment. [10] .

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