Experimental Adoptive Cell Therapy May Improve Outcomes in Soft Tissue Sarcomas

Treating soft tissue sarcomas poses significant challenges, but a recent international phase 2 study published in The Lancet suggests that afamitresgene autoleucel (Afami-cel), an adoptive cellular therapy, may improve outcomes in heavily pretreated patients.

Afami-cel is an autologous CD4-negative and CD8-positive T-cell product engineered with a self-inactivating lentiviral vector to express a high-affinity MAGE-A4-specific T-cell receptor. MAGE-A4 is expressed in solid tumors, including soft tissue sarcomas like synovial sarcoma and myxoid/round cell liposarcoma (MRCLS).

In the SPEARHEAD-1 trial, investigators evaluated a single-arm cohort of 52 patients with metastatic or unresectable synovial sarcoma (44 patients) or MRCLS (8 patients) with specific features. Patients received a single dose of afami-cel after undergoing lymphodepleting chemotherapy. The primary endpoint was overall response rate (ORR), with secondary endpoints being duration of response and safety.

Among all patients, the ORR was 37%, including 39% among patients with synovial sarcoma and 25% among patients with MRCLS. Investigators noted that the treatment response was rapid and that the median duration of response was 11.6 months and 4.2 months, respectively. Certain patient subgroups, such as females, those with lower disease burdens and synovial sarcoma patients expressing higher MAGE, exhibited higher response rates.  

While investigators observed adverse events (cytopenias and low-grade cytokine release syndrome), these were managed with standard treatments. There were no treatment-related deaths.

The study also highlighted the potential role of interferon-gamma as a biomarker associated with anti-tumor response, suggesting the need for continued research in identifying resistance biomarkers.