On January 31, 2018, Duke Cancer Institute joined a select group of medical centers across the country (34 to date) certified and trained to administer Yescarta, the first Food and Drug Administration-approved CAR T-cell therapy for the treatment of adult patients with certain types of relapsed or refractory non-Hodgkin’s lymphoma. Duke Cancer Institute is currently the only center in the region — South Carolina, North Carolina, and Virginia — offering this immunotherapy.

Chimeric antigen receptor T-cell therapy, better known as CAR T-cell therapy, is unlike any other cancer treatment. The individualized gene therapy transforms a patient’s own T-cells (white blood cells) into CAR T-cells designed to recognize, attack, and destroy cancerous B cells.

“With CAR T-cells, using the patient's own immune system to fight cancer has become a reality,” said Director of DCI’s Hematologic Malignancies & Cellular Therapy Program, Nelson Chao, MD, MBA. “The early data has been very encouraging and exciting.”

Manufactured by Kite Pharma, a Gilead company, Yescarta is the brand name for axi-cel (the short name for axicabtagene ciloleucel), which is FDA-approved to treat patients who have not responded to treatment or who have relapsed after receiving two or more other forms of systemic treatment for the following types of non-Hodgkin lymphomas (large B-cell lymphomas):

• Diffuse Large B-cell Lymphoma (DLBCL) not otherwise specified
• Primary Mediastinal Large B-cell Lymphoma (PMBCL)
• High-Grade B-cell Lymphoma
• DLBCL arising from Follicular Lymphoma (FL)

It is not indicated for the treatment of patients with Primary Central Nervous System (CNS) Lymphoma.

Eligibility & Treatment

Patient eligibility for Yescarta therapy depends on several factors. Based on a comprehensive evaluation, patients may be offered a consultation with a doctor who specializes in this therapy or offered other lymphoma treatment options that are better suited to their health situation, including active surveillance, radiation therapy, targeted therapy, chemotherapy, and/or stem cell or bone marrow transplant. The Hematologic Malignancies and Cellular Therapy program also offers a variety of clinical trials for the treatment of lymphomas including other investigational CAR T-cell therapies.

If patients are appropriate for Yescarta therapy, approval is sought from their medical insurance provider. Once approved, they will visit the Adult Blood & Marrow Transplant (ABMT) Clinic, located at Duke’s North Pavilion, where they will undergo apheresis, a relatively painless four-hour outpatient procedure in which white blood cells (T cells) are removed from the bloodstream to be used to manufacture Yescarta. The collected cells are immediately walked down the hall to the Stem Cell Lab where the cells are frozen, packaged, and then shipped out the same day to Kite’s state-of-the-art commercial manufacturing facility in El Segundo, CA. There the cells will be re-engineered, frozen again, and shipped right back to Duke — about a 17-day process.

Five days before the patient is to be infused with their “new” cells at Duke University Hospital (Inpatient Unit 9100), they undergo three consecutive days of lymphodepleting chemotherapy at the ABMT Clinic, followed by a day of rest. Then the patient is admitted to the hospital. The following day, they receive their autologous infusion and stay in the hospital for about seven days for active surveillance. Following this, they are monitored daily, as an outpatient, at the ABMT Clinic for the next four weeks. (Patients must commit to staying within a half-hour radius during this time. They are given contact information for local apartment options as well as rooms at the DCI-affiliated “home away from home” Caring House.)

Chao warns that the highly specialized and highly personalized therapy is not without its serious risks — high fever, serious flu-like symptoms, sudden drops in blood pressure, and seizures, but points out that “it’s an exciting step forward in providing a potentially curative option for patients that have failed other forms of treatment.”

So far there are a handful of patients under evaluation at Duke for the Yescarta therapy.

At Duke, A CAR T Future

As a National Cancer Institute-designated Comprehensive Cancer Center, DCI’s Hematologic Malignancies & Cellular Therapy specialists treat 1,000 people with blood cancer each year, more than any other facility in North Carolina. It was this high level of expertise coupled with Duke’s pre-existing infrastructure, that enabled Duke to be certified to offer Yescarta following FDA approval.

“Duke has had a long history of focusing on immune-based therapies, developing various cancer vaccines, remaining on the cutting edge of allogenic transplant immune therapy, and now involvement in multiple monoclonal antibody and engineered T-cell immuno-based therapies,” said Hematologic Malignancies section chief David Rizzieri, MD. “Harnessing the power of one’s own immune system to attack cancer has been a goal for decades. It allows us to turn from standard chemotherapy to targeted immune stimulation using the body’s own normal defense mechanisms. This is just the first step of many in the next few years that will allow us to take an entirely new direction in cancer therapy to improve outcomes.”

Duke Cancer Institute’s Hematologic Malignancies and Cellular Therapy program is actively building other CAR T-cell clinical trials, for the treatment of various other hematologic malignancies in adults. At present, there will be no staffing up required to deploy this therapy, but that could change in the future. Hematologic malignancies and cellular therapy specialist Ahmed Galal, MD, FRACP, MSc is the clinical lead for CAR T-cell therapy.

“CAR T-cell therapy has the potential to revolutionize cancer care,” said administrative director of the Hematologic Malignancies & Cellular Therapy Program, Gabriel Alcantara. “This is only the first adult commercial CAR T-cell therapy at Duke. While it’s starting out, for adults, in certain types of non-Hodgkin’s lymphomas, there will be more CAR T therapies in the next few years for other blood cancers, and further down the road, to solid tumor types.”

Duke is also already in the process of becoming certified to administer tisagenlecleucel (brand name: Kymriah, manufactured by Novartis) — the first CAR T-cell therapy FDA-approved for the treatment of patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) who didn’t respond to treatment or relapsed at least twice — and was one of the sites that participated in the clinical trial that led to its approval.

Patients who are interested in being evaluated for adult CAR-T cell therapy must have their physician provide a referral.