KYMRIAH (tisagenlecleucel) For Treatment of B-cell precursor acute lymphoblastic leukemia (ALL)
INDICATIONS AND USAGE
KYMRIAH is a CD19-directed genetically modified autologous T-cell immunotherapy 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.
- Adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.
Limitation of Use: KYMRIAH is not indicated for the treatment of patients with primary central nervous system lymphoma.
MECHANISM OF ACTION
KYMRIAH is a CD19-directed genetically modified autologous T cell immunotherapy that 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 that 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.
Pharmacodynamics: Due to the on-target effect of KYMRIAH, a period of B-cell aplasia is expected. Among evaluable pediatric and young adult r/r B-cell ALL patients with an ongoing response at Month 24, 33% had no detectable B cells at baseline prior to infusion. At Month 24, 88% had no detectable B cells. Most adult r/r DLBCL patients had B-cell depletion at baseline prior to infusion due to previous treatment with rituximab. Recovery of B-cell levels were observed with longer follow-up in some of the responding DLBCL patients after KYMRIAH infusion. Among evaluable adult r/r DLBCL patients with an ongoing response at Month 24, all patients had no detectable B cells at baseline prior to infusion or at Month 24.
DOSAGE AND ADMINISTRATION
- For autologous use only. For intravenous use only.
- Administer a lymphodepleting regimen if needed before infusion of KYMRIAH.
- Do NOT use a leukodepleting filter.
- Verify the patient’s identity prior to infusion.
- Premedicate with acetaminophen and an H1-antihistamine.
- Confirm availability of tocilizumab prior to infusion.
- Dosing of KYMRIAH is based on the number of chimeric antigen receptor (CAR)-positive viable T cells.
Pediatric and Young Adult B-cell ALL (up to 25 years of age)
- For patients 50 kg or less, administer 0.2 to 5.0 x 106CAR-positive viable T cells per kg body weight intravenously.
- For patients above 50 kg, administer 0.1 to 2.5 x 108 total CARpositive viable T cells (non-weight based) intravenously.
Adult Relapsed or Refractory Diffuse Large B-cell Lymphoma
- Administer 0.6 to 6.0 x 108 CAR-positive viable T cells intravenously.
DOSAGE FORMS AND STRENGTHS
Pediatric and Young Adult B-cell ALL (up to 25 years of age) A single dose of KYMRIAH contains 0.2 to 5.0 x 106 CAR-positive viable T cells per kg of body weight for patients 50 kg or less, or 0.1 to 2.5 x 108 CARpositive viable T cells for patients more than 50 kg, suspended in one to three patient-specific infusion bag(s) for IV infusion.
Adult Relapsed or Refractory Diffuse Large B-cell Lymphoma A single dose of KYMRIAH contains 0.6 to 6.0 x 108 CAR-positive viable T cells suspended in one to three patient-specific infusion bag(s) for IV infusion.
WARNINGS AND PRECAUTIONS
- Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion.
- Serious Infections: Monitor patients for signs and symptoms of infection; treat appropriately.
- Prolonged Cytopenias: Patients may exhibit ≥ Grade 3 cytopenias for several weeks following KYMRIAH infusion. Prolonged neutropenia has been associated with an increased risk of infection.
- Hypogammaglobulinemia: Monitor and provide replacement therapy until resolution. Assess immunoglobulin levels in newborns of mothers treated with KYMRIAH.
Pediatric and Young Adult B-cell ALL (up to 25 years of age): The most common adverse reactions (incidence greater than 20%) are cytokine release syndrome, infections-pathogen unspecified, hypogammaglobulinemia, fever, decreased appetite, viral infectious disorders, headache, febrile neutropenia, bleeding episodes, vomiting, encephalopathy, diarrhea, hypotension, cough, nausea, bacterial infectious disorders, pain, hypoxia, fatigue, acute kidney injury, and arrhythmia.
Adult Relapsed or Refractory Diffuse Large B-cell Lymphoma: The most common adverse reactions (incidence greater than 20%) are CRS, infections pathogen unspecified, fever, diarrhea, nausea, fatigue, hypotension, edema, bleeding episodes, dyspnea, and headache.
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