Kymriah (tisagenlecleucel)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.


Approval Status:

Approved August 2017

Specific Treatments:

refractory B-cell precursor acute lymphoblastic leukemia

Therapeutic Areas

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General Information

Kymriah (tisagenlecleucel) is a CD19-directed genetically modified autologous T cell immunotherapy.

Kymriah is specifically indicated for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Kymriah is supplied as a suspension for intravenous infusion. Prior to infusion: premedicate with acetaminophen and an H1-antihistamine and confirm the availability of tocilizumab in the event of a CRS reaction. Dosing is based on the number of chimeric antigen receptor (CAR) positive viable T cells. For patients 50 kg or less, administer 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight intravenously. For patients above 50 kg, administer 0.1 to 2.5  x 10(8) total CAR-positive viable T cells (non-weight based) intravenously. 

Clinical Results

FDA Approval

The FDA approval of Kymriah was based on an open-label, multicenter single-arm trial in pediatric and young adults with R/R B-cell precursor ALL. In total, 88 subjects were enrolled and 63 were evaluable for efficacy. Treatment consisted of lymphodepleting chemotherapy (fludarabine 30 mg/m2 daily for 4 days and cyclophosphamide 500 mg/m2 daily for 2 days) followed by a single dose of Kymriah. Of the 22 patients who had a WBC count < 1000/µL, 20 received lymphodepleting chemotherapy prior to Kymriah while 2 received Kymriah infusion without lymphodepleting chemotherapy. Fifty-three patients received bridging chemotherapy between time of enrollment and lymphodepleting chemotherapy.  The efficacy of Kymriah was established on the basis of complete remission (CR) within 3 months after infusion, the duration of CR, and proportion of patients with CR and minimal residual disease (MRD) < 0.01% by flow cytometry (MRD-negative). Among the 63 infused patients, 52 (83%) achieved CR/CRi, all of which were MRD-negative. With a median follow-up of 4.8 months from response, the median duration of CR/CRi was not reached (range: 1.2 to 14.1+ months). Median time to onset of CR/CRi was 29 days with onset of CR/CRi between 26 and 31 days for 50/52 (96%) responders. The stem cell transplantation rate among those who achieved CR/CRi was 12% (6/52).

Side Effects

Adverse effects associated with the use of Kymriah may include, but are not limited to, the following:

  • cytokine release syndrome
  • hypogammaglobulinemia
  • infections-pathogen unspecified
  • pyrexia
  • decreased appetite
  • headache
  • encephalopathy
  • hypotension
  • bleeding episodes
  • tachycardia
  • nausea
  • diarrhea
  • vomiting
  • viral infectious disorders
  • hypoxia
  • fatigue
  • acute kidney injury
  • delirium

The Kymriah label comes with the following Boxed Warning:

  • Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Kymriah. Do not administer Kymriah to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab.
  • Neurological toxicities, which may be severe or life-threatening, can occur following treatment with Kymriah, including concurrently with CRS. Monitor for neurological events after treatment with Kymriah. Provide supportive care as needed.
  • Kymriah is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Kymriah REMS. 


Mechanism of Action

Kymriah (tisagenlecleucel) is a CD19-directed genetically modified autologous T cell immunotherapy  which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The CAR is comprised of a murine single-chain antibody fragment which recognizes CD19 and is fused to intracellular signaling domains from 4-1BB (CD137) and CD3 zeta. The CD3 zeta component is critical for initiating T-cell activation and antitumor activity, while 4-1BB enhances the expansion and persistence of Kymriah. Upon binding to CD19-expressing cells, the CAR transmits a signal to promote T-cell expansion, activation, target cell elimination, and persistence of the Kymriah cells

Additional Information

For additional information regarding Kymriah or refractory B-cell precursor acute lymphoblastic leukemia, please visit