When it comes to battling a rare and aggressive cancer like synovial sarcoma, the treatment options have often been limited—until now. The FDA’s recent approval of Tecelra (Amafi-Cel), the first gene therapy for adults with metastatic synovial sarcoma, not only provides new hope for patients who’ve exhausted other options but also paves the way for other innovative cell therapies emerging in clinical trials. These therapies are specifically targeting synovial sarcomas and myxoid/round liposarcomas, highlighting a promising future in the treatment landscape for these challenging sarcomas.
What is Synovial Sarcoma and Myxoid/Round Liposarcoma?
Synovial sarcoma is a rare and aggressive type of soft tissue sarcoma that accounts for approximately 5-10% of all soft tissue sarcomas. Despite its name, it does not typically originate in the synovial tissues of joints but can occur near them, as well as in other areas of the body.
Myxoid/round cell sarcoma, commonly referred to as myxoid liposarcoma, is a subtype of liposarcoma, which is a malignant tumor of fat tissue. Myxoid/round cell liposarcoma accounts for approximately 20% to 30% of all liposarcoma cases. In the broader context of all soft tissue sarcomas, myxoid/round cell liposarcoma represents about 10% to 15% of the cases. It is characterized by its unique histological features and behavior.
What are the differences?
Traditional Treatment
- Surgery: The primary treatment is surgical removal of the tumor with clear margins to minimize the risk of recurrence. Risk is recurrence after surgery is approximately 38%
- Radiation Therapy: Often used before or after surgery to shrink the tumor or kill any remaining cancer cells.
- Chemotherapy: May be used, particularly if the cancer has spread (metastasized) or is high-grade.
- Targeted Therapy: Ongoing research into targeted therapies and immunotherapies holds promise for future treatments.
Although current literature suggests the five-year survival rates for sarcoma ranges from 59–75% there is still a potential risk of recurrence and metastasis following traditional therapies. Two new treatments have emerged for the treatment of synovial sarcomas and Myxoid/Round Liposarcomas called Tecelra (Amafi-cel) and Lete-cell.
New potential treatments
Lete-cel (lete-cel) and Tecelra (amafi-cel) are both types of T-Cell Receptor (TCR) Cell Therapies, but they differ in their targets and clinical applications. TCR therapy is a personalized cancer treatment that modifies a patient’s own T cells to target and destroy cancer cells. This innovative approach has shown significant success in treating certain types of blood cancers, such as leukemia and lymphoma, and is now showing great promise in the solid tumor arena.
FDA APPROVED- AUG 2024
Tecelra (Amafi-Cel)
- Target Antigen: MAGE-A4
- Indication: Amafi-cel is being developed for the treatment of various types of cancer, including solid tumors such as non-small cell lung cancer (NSCLC), head and neck cancers, and certain sarcomas.
- Mechanism of Action: Amafi-cel targets the MAGE-A4 antigen, which is also expressed on the surface of certain cancer cells. The binding of amafi-cel to its target antigen activates the CAR T-cells to attack and destroy the cancer cells.
Recent Results:
- 43.2% overall response rate among patients who had already undergone other treatments
- 39% of patients who received afami-cel in the pivotal SPEARHEAD-1 trial had clinical responses with a median duration of response of ~12 months.
- Median overall survival (mOS) was ~17 months in SPEARHEAD-1 compared to historical mOS of <12 months for people with synovial sarcoma who received two or more prior lines of therapy.
- 70% of people with advanced synovial sarcoma who respond to afami-cel are alive two years post-treatment
- The U.S. Food and Drug Administration (FDA) accepted priority review of afami-cel, for advanced synovial sarcoma and the application received FDA approval for commercial use on August 1, 2024.
Other Ongoing Clinical Trials
Lete-cel (Letetresgene Autoleucel)
- Target Antigen: NY-ESO-1
- Indication: Lete-cel is primarily being investigated for the treatment of certain solid tumors, including synovial sarcoma and myxoid/round cell liposarcoma.
- Mechanism of Action: Lete-cel is designed to recognize and bind to the NY-ESO-1 antigen, which is expressed on the surface of some cancer cells. Upon binding, the CAR T-cells are activated and initiate an immune response to kill the cancer cells.
Recent Results: Recent data released at the 2024 ASCO meeting showed a 40% overall response rate with a median duration of response 10.6 months, with several patients still having an ongoing response at the time of data release.
Clinical Implications
Both therapies represent significant advances in personalized cancer treatment, leveraging the patient’s own immune system to fight cancer cells that express specific antigens. This approach is important for several reasons:
- Personalization: By using a patient’s own T cells, cell therapy is highly tailored to their specific cancer, increasing the likelihood of an effective response.
- Precision Targeting: The engineered T cells are designed to recognize and attack cancer cells with specific antigens, minimizing damage to healthy cells and reducing side effects compared to traditional treatments.
- Potential for Long-Term Remission: TCR cells can persist in the body and continue to target cancer cells over time, offering the possibility of long-term disease control and even cure in some cases.
- Effectiveness for Hard-to-Treat Cancers: TCR therapy has shown remarkable success in treating certain types of blood cancers that are resistant to other treatments, providing new hope for patients with limited options.
Overall, TCR therapy exemplifies the shift towards more individualized and targeted cancer treatments, offering promising outcomes for patients with challenging or previously untreatable cancers.
Currently there are ongoing trials using TCR cells for the treatment of synovial sarcoma and Myxoid/Round Liposarcoma. For more information on this visit www.clinicaltrials.gov
About the Author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.