First engineered T-cell therapy approved for solid tumors
An engineered T-cell therapy, afamitresgene autoleucel (afami-cel), has received FDA approval for the treatment of synovial sarcoma following recent promising clinical trial results.
Synovial sarcoma is a rare type of cancer, characterized by solid tumors that begin in the body’s soft tissue, often the joints. The current standard of treatment is surgery, often combined with radiotherapy and/or chemotherapy. But this is not always successful, leaving patients with limited treatment options, particularly in cases where the cancer metastases to other parts of the body.
The emergence of T-cell therapies has offered new avenues for the treatment of rare cancers like synovial sarcoma. Afami-cel, marketed as Tecelra, is one type of engineered cell therapy called a T-cell receptor (TCR) therapy. Like the better-known chimeric antigen receptor (CAR) T-cell therapy, TCR therapy works by extracting patients’ T-cells and engineering them to recognize cancer cells, before reinfusing them back into the patient, where they can detect and attack tumors. However, while CAR-T therapies rely on the recognition of receptors on the outside of cancer cells, TCR therapies are engineered to identify markers hidden within cancer cells. Afami-cel is designed to recognize a protein called MAGE-A4, which has particularly high expression in tumors.
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Afami-cel’s FDA approval comes following the results from the first cohort in an ongoing Phase II clinical trial, led by Sandra D’Angelo and her team at Memorial Sloan Kettering Cancer Center (MSK; NY, USA). The study is testing afami-cel in participants at 23 sites across Canada, Europe and the USA. The initial cohort contained 52 adult participants with synovial sarcoma and myxoid/round cell liposarcoma, another type of soft tissue sarcoma, who had not responded to other treatments. After a single treatment dose, over a third of participants (37%) saw a reduction in tumor volume. In patients with synovial sarcoma, the treatment remained effective for an average of 11.6 months, while patients with myxoid/round cell liposarcoma responded for 4.2 months on average. According to D’Angelo, “Some patients in the trial had their tumors completely disappear and have not had the cancer come back for several years.”
Despite its promising results, the treatment was not without notable side effects. The majority of patients (71%) experienced cytokine release syndrome, a common event seen with immunotherapy where the body’s immune system reacts strongly to treatment and goes into temporary overdrive. Additionally, almost all participants saw a drop in their blood cell counts – an effect that is attributable to the chemotherapy patients receive prior to administration of the T-cell therapy. None of these adverse effects were fatal, but they still represent an important consideration when managing patients receiving afami-cel.
“These findings are significant for a group of patients who have largely exhausted other treatment options,” explains D’Angelo. On the approval, she notes, “This treatment offers an important new option for people with this rare cancer… It is also an important step forward in the development of T cell therapies for solid tumors, which has been a major challenge.”
The team is hopeful that the treatment will eventually be approved for a number of MAGE-A4-expressing solid tumors.
