The US Food and Drug Administration (FDA) recently approved tisagenlecleucel (Kymriah) for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse in pediatric and young adult patients (up to age 25 years). Tisagenlecleucel, from Novartis Pharmaceuticals Corp, is the first chimeric antigen receptor (CAR) T cell immunotherapy to be granted approval. The agent consists of autologous T cells collected via leukapheresis that are genetically modified with a new gene containing a CAR protein. The modified T cells identify and eliminate both malignant and normal cells expressing CD19.1

The approval is based on a single-arm trial of 63 patients with relapsed or refractory pediatric precursor B-cell ALL, including 35 patients who had undergone prior hematopoietic stem-cell transplantation, in which overall response rate was 82.5% (63% of patients achieved complete remission and 19% achieved complete remission with incomplete hematologic recovery).

Tisagenlecleucel is administered in a single IV dose. Recommended dose is 1 infusion of 0.2 to 5.0 × 106 CAR-positive viable T cells per kg body weight for patients who weigh 50 kg or less and 0.1 to 2.5 × 108 total CAR-positive viable T cells intravenously for patients who weigh more than 50 kg, administered 2 to 14 days after completion of lymphodepleting chemotherapy.

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The most common adverse reactions (occur in more than 20% of patients) are cytokine release syndrome (CRS), hypogammaglobulinemia, infections-pathogen unspecified, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding episodes, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, fatigue, acute kidney injury, and delirium. Eighty-four percent of patients experienced grade 3 or 4 adverse events.

Serious adverse reactions reported in patients receiving tisagenlecleucel included CRS (fatal CRS and CRS-associated disseminated intravascular coagulation with intracranial hemorrhage), prolonged cytopenia, infection, cardiac failure, and cardiac arrest. Tisagenlecleucel is approved with a Risk Evaluation and Mitigation Strategy (REMS).1

In a separate announcement, US FDA granted approval to tocilizumab (Actemra) for the treatment of CAR T cell-induced severe or life-threatening CRS in patients ages 2 years and older. Tocilizumab is a humanized interleukin-6 (IL-6) receptor antagonist approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis that is unresolved after 1 or more disease-modifying antirheumatic drugs.2

Approval is based on a retrospective analysis of pooled outcome data from clinical trials of CAR T cell therapy for blood cancers. The analysis included 45 pediatric and adult patients who experienced severe or life-threatening CRS treated with tocilizumab. Cytokine release syndrome is caused by an overactive immune response and has been identified as a severe and potentially life-threatening adverse effect of CAR T cell therapy.

Potentially fatal serious adverse events with tocilizumab include greater risk for infection or worsening of any existing infection. Additional adverse effects include stomach tears; altered blood test results (ie, low neutrophil and platelet counts, increases in certain liver function test levels and blood cholesterol levels); increased risk of certain cancers; hepatitis B infection; serious allergic reactions, including death; and nervous system problems.2

Tisagenlecleucel is manufactured by Novartis Pharmaceuticals Corporation, and tocilizumab is manufactured and distributed by Genentech.


1. FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome [news release]. Silver Spring, MD: US Food and Drug Administration; last updated September 5, 2017. Accessed September 5, 2017.

2. FDA approves Genentech’s Actemra (tocilizumab) for the treatment of CAR T cell-induced cytokine release syndrome [news release]. South San Francisco, CA: Genentech; August 30, 2017. Accessed September 5, 2017.