What is the role of axicabtagene ciloleucel (Yescarta) in chimeric antigen receptor (CAR) T-cell therapy?

Answer

The second CAR T-cell therapy to enter clinical practice, axicabtagene ciloleucel (Yescarta), was approved by the FDA in October 2017. Axicabtagene ciloleucel is CD19-directed with a CD28 co-stimulatory molecule and is indicated for use in adults with DLBCL who have not responded to or who have relapsed after at least two other lines of therapy. Approved uses include DLBCL, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Axicabtagene ciloleucel is not indicated for the treatment of primary central nervous system lymphoma.^[13]

The ZUMA-1 trial in refractory aggressive non-Hodgkin lymphoma (DLBCL, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma) enrolled 111 patients, 101 of whom received axicabtagene ciloleucel. The objective response rate (ORR)—consistent across disease subtypes and other key covariates—was 82%.^[14]At a median follow up of 27.1 months, 83% of patients had a response and 58% had a complete response. The median duration of response was 11.1 months and the median overall survival was not reached.^[15]

Since the approval of axicabtagene ciloleucel, data in patients treated outside of clinical trials have become available. These data show that patients treated in the “real world” have outcomes similar to those reported in the ZUMA-1 trial, with approximately 40-50% of patients remaining in remission at 12 months. Patients with a baseline high lactate dehydrogenase level or poor performance status were found to have the highest risk of progression or death after CAR T-cell therapy.^{[16, 17]}

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Sameh Gaballa, MD, MS Assistant Member, Division of Malignant Hematology, Moffitt Cancer Center

Sameh Gaballa, MD, MS is a member of the following medical societies: American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Michael D Jain, MD, PhD Assistant Member, Clinician Investigator Track, Blood and Marrow Transplant and Cellular Immunology, Moffitt Cancer Center; Assistant Professor, Department of Oncological Sciences, University of South Florida Morsani College of Medicine

Michael D Jain, MD, PhD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Matthew H Carabasi, MD Professor and Vice Chair of Outreach, Director, Medical Oncology Specialty Network, Department of Medical Oncology, Sidney Kimmel Medical College of Thomas Jefferson University; Senior Director, Strategic Oncology Partnerships, Jefferson Health, Sidney Kimmel Cancer Center

Matthew H Carabasi, MD is a member of the following medical societies: American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Usama Gergis, MD, MBA Professor of Oncology, Sidney Kimmel Medical College of Thomas Jefferson University; Director, Bone Marrow Transplant and Immune Cellular Therapy, Department of Medical Oncology, Division of Hematological Malignancies, Sidney Kimmel Cancer Center

Usama Gergis, MD, MBA is a member of the following medical societies: American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, Center for International Blood and Marrow Transplant Research, Eastern Mediterranean Blood and Marrow Transplantation, European Society for Blood and Marrow Transplantation

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Pierluigi Porcu, MD Professor of Medical Oncology, Professor of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College of Thomas Jefferson University; Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Tranplantation, Sidney Kimmel Cancer Center

Pierluigi Porcu, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, Cutaneous Lymphoma International Consortium, International Society for Cutaneous Lymphomas, National Comprehensive Cancer Network, Society for Investigative Dermatology, US Cutaneous Lymphoma Consortium

Disclosure: Nothing to disclose.

What is the role of axicabtagene ciloleucel (Yescarta) in chimeric antigen receptor (CAR) T-cell therapy?

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