Expert Clinical Network Insights: October 2024 - Prime Therapeutics
Metastatic Synovial Sarcoma
Medication insights: afamitresgene autoleucel (Tecelra)
Efficacy, safety and patient experience
Synovial sarcoma is a rare and aggressive form of soft tissue sarcoma. Current treatment options for advanced synovial sarcoma are limited. Prior to the approval of afamitresgene autoleucel (afami-cel), the treatment landscape consisted of oral therapies, each of which has minimal efficacy. However, it is difficult to assess how this gene therapy compares to these current treatment options for patients with advanced synovial sarcoma. Due to the rarity of the disease, a randomized trial for further evaluation of therapeutic efficacy is unlikely. The value of this gene therapy has been shown by some responders in the clinical trial who are benefiting from therapy, which is noteworthy because the approval of this treatment option is based on the benefit seen in these study responders.Based on the clinical trial, there are certain expectations for how long patients can anticipate seeing the benefits of treatment. The median duration of response was 11.6 months (95% CI, 4.4 to 18.0) in patients with synovial sarcoma and 4.2 months (95% CI, 2.9 to 5.5) in patients with myxoid round cell liposarcoma. Responses were observed across key subgroup covariates. The median overall survival was 15.4 months (95% CI, 10.9 to 28.7) in the overall population, with an overall survival probability of 60% (95% CI, 46 to 73) at 12 months. Median overall survival was not reached (95% CI, 15.4 – not estimable) in patients with synovial sarcoma with a Response Evaluation Criteria in Solid Tumors (RECIST) response. The estimated overall survival probability for patients with synovial sarcoma and a RECIST response was 90% (95% CI, 65 to 99) at 12 months and 70% (95% CI, 43 to 87) at 24 months. All 52 patients who received afami-cel had treatment-emergent adverse effects, and 92% of patients had adverse effects related to treatment,2,3 with cytopenias being the most common grade 3 or worse adverse events. Cytokine release syndrome (CRS) did occur in most patients but were mostly grade 1-2 and manageable with standard treatments. For the most part, afami-cel has shown a manageable safety profile in clinical trials.
Before afami-cel treatment, a lymphodepleting regimen of cyclophosphamide and fludarabine must be administered. Then, a patient’s T cells are genetically modified to target and destroy cancer cells expressing the MAGE-A4. It is a complex therapy that involves leukapheresis of the patient’s peripheral blood mononuclear cells (PBMCs), genetic modification to transduce PBMCs with a lentiviral vector containing the MAGE-A4 TCR transgene, and then expanding the modified T cells and infusing them back into the patient. These engineered T cells then bind to MAGE-A4 on cancer cells, leading to their destruction by the immune system. The whole process can be quite complex and may require multiple hospital stays, though the exact number and duration of inpatient stays can vary depending on individual circumstances. Due to the specialized nature of this treatment, it is only administered at select cancer centers that have the necessary infrastructure and expertise. While the exact number of centers offering this therapy varies by region, it is a limited number. Despite the complex treatment process, afami-cel offers a significant advancement in cancer treatment.
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- FDA Approves Nonsteroidal Treatment for Duchenne Muscular Dystrophy. August 2, 2024. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-metastatic-synovial-sarcoma. Accessed September 6, 2024.
- D'Angelo SP, Araujo DM, Abdul Razak AR, et al. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial. Lancet. 2024; 403(10435): 1460-1471. DOI: 10.1016/S0140-6736(24)00319-2.
- D'Angelo SP, Druta M, Van Tine BA, et al. Primary efficacy and safety of letetresgene autoleucel (lete-cel; GSK3377794) pilot study in patients with advanced and metastatic myxoid/round cell liposarcoma (MRCLS). Meeting abstract 11500: American Society of Clinical Oncology: 2022 ASCO Annual meeting. J Clin Oncol. (40)16. https://doi.org/10.1200/JCO.2022.40.16_suppl.11500.
- Mangla A, Gasalberti DP. Synovial Cell Sarcoma. Updated 2023 May 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK587366/. Accessed September 6, 2024.
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