T-Cell Receptor Therapy Available for Segment of Population with Synovial Sarcoma

This spring, Cleveland Clinic Cancer Institute became one of the only centers locally that’s authorized to administer afamitresgene autoleucel (afami-cel) a newly FDA-approved cell therapy for adults with advanced synovial sarcoma. Amafi-cell has shown efficacy specifically in patients with synovial sarcoma whose tumors express the melanoma-associated antigen-A4 (MAGE-A4). It is the first FDA-approved cell therapy for any solid tumor.

Background

Synovial sarcomas can be incredibly aggressive. “These tumors frequently metastasize and when they do, the current chemotherapy regimens are not very effective,” explains Dale Shepard, MD, PhD, a medical oncologist and Co-Director of the Cleveland Clinic Sarcoma Program. “Survival rates have historically been low.”

To address this gap, a team of researchers conducted a phase 2 trial of the genetically modified autologous T-cell immunotherapy afami-cel with patients in Canada, Europe and the U.S. Of the 52 patients enrolled in the study, 39% experienced a response, including two patients who had a complete response. Of the patients who responded, the median duration of response was roughly one year.

For the most part, the treatment was well tolerated. Side effects included low-grade cytokine release syndrome and prolonged blood count suppression. “With similar treatments like T-cell therapy we worry about neurological toxicity and that was not reported in this trial,” notes Dr. Shepard.

This small randomized trial led to FDA approval of the T-cell therapy in adults with unresectable or metastatic synovial sarcoma. Amafi-cell is effective specifically for the 25-30% of patients with synovial sarcoma who have the HLA subtype that expresses the MAGE-A4 protein.

Treatment delivery

Immune effector T-cell receptor therapy is a different immune mechanism than CAR T-cell therapy. While CAR T-cell therapy can recognize antigens that exist on the cell surface, T-cell receptor therapies can target proteins within a cell. This is advantageous because often solid tumors differ on the intracellular level from normal cells.

However, the delivery mechanism is similar to CAR T-cell therapy in that amafi-cell is derived from a patient’s own T cells. The process involves:

• Collecting T cells from the patient
• Sending the patient’s T cells to the manufacturer, who injects them with a viral vector to allow for better recognition and binding to the MAGE-A4 protein that’s expressed in the cancer cells
• Administering low-dose chemotherapy to reduce the patient’s lymphocyte count
• Reinfusing the T cells back into the patient
• Monitoring the patient for side effects

Cleveland Clinic wasn’t a participant in the trial but has added amafi-cell to its expanding portfolio of cell therapies. As a major academic center, Cleveland Clinic has the infrastructure and experience to deliver these complex treatments.

“The process - from identifying a patient through getting the T-cells manufactured - is about four to six weeks. That’s an important consideration for patient selection, particularly if you have a patient with rapidly progressing disease,” says Dr. Shepard, who is available to consult with referring physicians about recommending treatment options for any type of sarcoma and identifying patient eligibility for this cell therapy.

Amafi-cell can be administered to patients at Cleveland Clinic's Blood and Marrow Transplant and Cell Therapy at the hospital’s main campus. Clinicians hope to be able to deliver the therapy on an outpatient basis in the future.

What’s next

The study data so far indicates patients with higher levels of MAGE-A4 and lower disease burden tended to achieve better responses. As Cleveland Clinic builds up its experience with amafi-cell, it’s looking to gather data to identify which patients are appropriate for the treatment and most likely to experience a response.