ACCELERATED approval to afamitresgene autoleucel (amfi-cel) for the treatment of adult patients with unresectable or metastatic synovial sarcoma has recently been granted by the FDA.
This is based on results from the Phase 2 SPEARHEAD-1 trial. The open-label, nonrandomized SPEARHEAD-1 trial enrolled patients aged 16 to 75 with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma, confirmed via cytogenetics to express MAGE-A4. Eligibility required positivity for specific HLA-A02 alleles, excluding HLA-A02:05, measurable disease per RECIST 1.1, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. All participants had received at least one prior line of anthracycline- or ifosfamide-containing chemotherapy.
The results demonstrated a 43% overall response rate in patients with unresectable or metastatic synovial sarcoma. Complete response was observed in 4.5% of patients, and the median duration of response was 6 months. These findings offer hope to patients with limited treatment options, especially in a field where therapeutic advancements have been sparse.
For clinicians, the management of patients receiving afami-cel will require vigilance due to potential adverse effects. The most notable of these is cytokine release syndrome (CRS), observed in 71% of trial participants, though only 2% experienced severe grade 3 CRS. All cases of CRS were successfully managed with tocilizumab, and in some instances, corticosteroids.
The FDA’s accelerated approval underscores the importance of genetic and molecular diagnostics in identifying eligible patients for this therapy. As oncologists, ensuring that patients meet the HLA and MAGE-A4 criteria will be crucial for optimal treatment outcomes. The ongoing development of related therapies suggests further opportunities for targeted treatments that may further enhance the therapeutic landscape for solid tumors.
Reference: D’Angelo SP 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):1460-71.
Author: Anaya Malik, AMJ
