CAR-T cell therapy for lymphoma and other blood cancers at Mayo Clinic in Jacksonville, Florida

Sept. 22, 2022

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Mohamed A. Kharfan Dabaja, M.D., M.B.A., is a hematologist and oncologist in the blood and marrow transplant and cellular therapy programs at Mayo Clinic in Jacksonville, Florida. He responds to questions about chimeric antigen receptor (CAR)-T cell therapy and its use in lymphoma treatment.

What is the CAR-T Cell Therapy Program?

Mayo Clinic was one of the centers treating patients in the clinical trial that led to approval of CAR-T cell therapy by the Food and Drug Administration (FDA). Our CAR-T Cell Therapy Program is one of the landmark programs throughout the country. We have experts trained and certified to manage this therapy.

We continue to learn new and innovative ways to use the therapy. Mayo Clinic is the only center in Jacksonville certified to perform CAR-T cell therapy, and the only such center in northeast Florida. Mayo Clinic is also one of the few centers in the nation offering clinical trials evaluating CAR-T cell therapy for solid tumors.

Which patients can CAR-T cell therapy help?

The FDA has approved CAR-T cell therapy for relapsed, refractory (RR) B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, multiple myeloma and B-cell acute lymphoblastic leukemia. Because of how fast these diseases can progress, patients generally should be referred to specialized centers as soon as they show lack of response to a second line therapy.

Patients with large B-cell lymphoma who do not respond to an anthracycline-based front-line chemoimmunotherapy or who show evidence of relapse within 12 months from their last dose of that front-line chemoimmunotherapy may be eligible for CAR-T cell therapy as a second line treatment because the FDA recently approved axicabtagene ciloleucel for that indication.

What advancements have been made in CAR-T cell therapy for lymphoma?

For lymphoma, several multicenter clinical trials were conducted in a heavily pre-treated population of patients.

  • ZUMA-1 led to the approval of axicabtagene ciloleucel for patients with RR large B-cell lymphoma (de novo or transformed) and primary mediastinal B-cell lymphoma. A five-year follow-up of the study showed over 40% of the patients were alive, representing a significant improvement in prognosis.
  • JULIET showed that a product called tisagenlecleucel resulted in impressive responses in RR large B-cell lymphoma, including complete remission.
  • TRANSCEND-NH-001 led to the approval of a third product, lisocabtagene maraleucel, for large B-cell lymphoma.
  • ZUMA-2 led to the approval of brexucabtagene autoleucel for RR mantle cell lymphoma.
  • ZUMA-7 led to the approval of axicabtagene ciloleucel for second line treatment of large B-cell lymphoma after showing better outcomes compared with chemoimmunotherapy and an autologous hematopoietic cell transplant.

The field continues to advance and evolve. Current research efforts are looking at using allogeneic CAR-T cells generated from healthy donors rather than collecting lymphocytes from the patient. This approach has the potential to make this therapy more readily available to patients.

How effective is CAR-T cell therapy for lymphoma?

The complete response rate has improved from 7% before CAR-T cell therapy to 40% to 54% after CAR-T cell therapy in patients with large B-cell lymphoma.

In the ZUMA-1 study, the objective response rate was 82%, and the complete response rate was 54%. In the JULIET study, the best overall response rate reported with tisagenlecleucel was 52%, and the complete response rate was 40%. In the Transcend-NH-001 study, the objective response rate was 73%, and the complete response rate was 53%. The ZUMA-2 study reported an objective response rate of 93% and a complete response rate of 67%.

For follicular lymphoma, the SCHOLAR-1 study was an international, multicohort retrospective non-Hodgkin lymphoma study that pooled data from two phase 3 clinical trials and from two observational cohorts. The pooled objective response rate was 26% and the complete response rate was 7%.

What does it look like to connect a patient with CAR-T cell therapy at Mayo Clinic?

Mayo Clinic in Florida is certified to prescribe all commercially available CAR-T cell therapy products. We evaluate the patient, confirm the diagnosis and ensure adequate vital organ function. Then the patient undergoes leukapheresis, and the patient's lymphocytes are transported to the manufacturing company for production.

Once Mayo Clinic receives the manufactured product, the patient receives chemotherapy for three days. This is typically for days -5, -4 and -3, and the product is infused on day 0. The patient is closely monitored in the hospital. In the future, it will be possible to monitor patients in an outpatient setting.

Our hematology and oncology experts work collaboratively with referring physicians for continuity of care. We are available to answer any treatment-specific questions and interpret disease-staging test results that arise after the patient's care is transferred. If you think CAR-T cell therapy might be right for your patient with lymphoma or any of these indications, we are here to help.

For more information

Refer a patient to Mayo Clinic.