Chimeric antigen receptor T-cell therapy: Foundational science and clinical knowledge for pharmacy practice

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• The Food and Drug Administration (FDA) has approved two novel autologous chimeric antigen receptor T-cell immunotherapies: tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™).
• These groundbreaking therapies target CD19-positive B-cell neoplasms, offering new hope for patients with advanced lymphocytic malignancies.

Purpose of the Study:

• To provide foundational scientific and clinical knowledge of chimeric antigen receptor T-cell immunotherapies.
• To detail common therapy-specific toxicities and Risk Evaluation and Mitigation Strategy (REMS) requirements for Kymriah™ and Yescarta™.
• To elucidate the role of pharmacists in managing these advanced therapies within multidisciplinary teams.

Main Methods:

• Review of scientific literature on chimeric antigen receptor T-cell therapy.
• Analysis of FDA-approved indications and safety profiles for Kymriah™ and Yescarta™.
• Examination of REMS protocols and their implications for pharmacy practice.

Main Results:

• Kymriah™ is indicated for relapsed/refractory acute lymphoblastic leukemia and large B-cell lymphoma; Yescarta™ is indicated for lymphoma.
• Both therapies carry risks of severe adverse events, including neurotoxicity and cytokine release syndrome, necessitating intensive supportive care.
• REMS protocols are mandated for both Kymriah™ and Yescarta™ due to significant safety concerns.

Conclusions:

• Chimeric antigen receptor T-cell immunotherapies represent a significant advancement in treating advanced B-cell malignancies.
• Understanding the complex toxicities and REMS requirements is crucial for safe and effective patient care.
• Pharmacists are integral to the successful implementation and management of these therapies, particularly in executing REMS programs.