Afami-cel’s Mechanism of Action and Role in Synovial Sarcoma

Edwin Choy, MD, PhD, director of the Sarcoma Program at the Division of Hematology Oncology at Massachusetts General Hospital, a founding member of Mass General Brigham, associate professor of medicine at Harvard Medical School, discusses the mechanism of action of afamitresgene autoleucel (afami-cel; Teclera) and the recent accelerated approval from the FDA for patients with advanced synovial sarcoma.

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0:09 | Afami-cel is a T-cell receptor therapy. What we do is we harvest the cell to the patient and then we modify the receptor to target a cancer protein called MAGE-A4. Once the T-cell receptor is genetically modified, we can re-infuse the T cells back into the cancer patient.

0:43 | In theory, these T cells can now target the tumor because they are attracted to the MAGE-A4 target. And it is a form of immunotherapy, so people can have the same type of [adverse] effects [AE] as seen with other immuno-therapeutic drugs. Cytokine release syndrome occurred in the majority of these patients to some degree. Most of them were grade 1 and 2. There was 1 patient with a grade 3 [AE], and then, one can also develop cytopenias with low neutrophils, lymphocytes. You can have other autoimmune type effects from this. But overall, I think the study found the treatment to be relatively tolerable, sort of in line with other T cell therapies.

1:47 | To even qualify for afami-cel, you have to meet 2 criteria. First of all, the disease itself has to express the target, otherwise treatment would be useless. You have to detect the tumor for MAGE-A4. I think the field is probably moving toward a standard operating procedure where all synovial sarcomas, once the diagnosis is made, will also be tested for MAGE-A4 expression in the same way others sarcomas, like GIST [gastrointestinal stromal tumor] is almost always tested for c-KIT expression. That is a target for GIST treatment. Similarly, we will look at synovial sarcoma as a MAGE-A4-expressing tumor that is amenable to this type of therapy.

2:39 | I think MAGE-A4 will be tested almost right off the bat by pathology. For the community and colleges, if you know your patients have synovial sarcoma, I would encourage testing early for something called HLA. HLA is the immunotype that will determine whether or not this product can be used or not at all for the patient. This product was developed for patients with specific HLA-A*02 subtypes. Maybe around 50% of the Caucasian population expresses HLA-A*02, and then less so in the non Caucasian population. I would encourage community oncologists to know a patient has the diagnosis to test early for both the HLA and the MAGE-A4.