Long-Term Survival of Patients with Advanced/Metastatic Synovial Sarcoma or Myxoid/Round Cell Liposarcoma Who Received the T-Cell Receptor T-Cell Therapy, Afamitresgene Autoleucel, in the Phase 2 Spearhead-1 Trial

Synovial sarcoma (SyS) and myxoid/round cell liposarcoma (MRCLS) are rare sarcoma subtypes, each representing 5–10% of soft tissue sarcomas , which typically express the intracellular cancer/testis antigen melanoma-associated antigen (MAGE) A4. Retrospective studies report median overall survival (OS) of 22.3 (95% CI: 19.7–24.1) months (mo) from metastasis diagnosis in SyS (Moreau-Bachelard C, ESMO Open 2022;7:100402), and of 16 (95% CI:13.5–18.9) mo and 26 (95% CI: 19.2–32.1) mo in SyS and MRCLS, respectively, from start of second-line therapy (Pollack SM, Cancer Med 2020;9:4593). Afamitresgene autoleucel (afami-cel) is a MAGE-A4–directed genetically modified autologous T-cell immunotherapy recently approved by the US Food and Drug Administration (FDA) for adults with unresectable/metastatic SyS who have received prior chemotherapy , are human leukocyte antigen (HLA)-A*02 eligible, and whose tumor expresses MAGE-A4 as determined by FDA-approved diagnostics. Afami-cel is infused into patients (pts) following lymphodepletion chemotherapy. Afami-cel met its primary efficacy endpoint in the Phase 2 open-label SPEARHEAD-1 trial (NCT04044768), in which 19/52 Cohort 1 pts with advanced/metastatic SyS or MRCLS had a response (D'Angelo SP, Lancet 2024;403:1460). Cytopenias were the most common Grade ≥3 adverse events . As of Aug 30, 2023, after a median follow-up time of 32.6 mo, median OS was 15.4 mo (95% CI: 10.9–28.7); follow-up is ongoing. Identify/characterize pts with advanced SyS or MRCLS who experienced long-term (∼3 year) survival post afami-cel and explore potential contributing factors. SPEARHEAD-1 was performed as described with 52 HLA-eligible pts with MAGE-A4–expressing advanced/metastatic SyS or MRCLS in Cohort 1. This survival analysis was ad hoc; formal statistical testing not performed. As of Jul 25, 2024, 13/52 (25%) Cohort 1 pts (12 with SyS, one with MRCLS) had OS >149 weeks (∼34 mo) after receiving afami-cel in Cohort 1 of SPEARHEAD-1. Baseline and treatment characteristics of the overall SPEARHEAD-1 Cohort 1 and of this subset of 13 long-term survivors are shown in the Table . Tumor expression of the target antigen, MAGE-A4, measured by immunohistochemistry , was slightly higher in this subset; previous lines of therapy and number receiving bridging therapy were slightly lower. Twelve of 13 had best overall response of partial response; one had stable disease. Cytokine release syndrome (CRS) occurred at similar levels in the overall cohort 1 of 52 pts (37 [71%] pts, with one Grade 3 event) and in the subset of 13 pts (nine [69%] pts, at Grade 1 in seven, Grade 2 in two). To date, survival of ∼3 years after treatment with afami-cel has been observed in 25% of pts with advanced/metastatic SyS or MRCLS in Cohort 1 of SPEARHEAD-1; work is ongoing to delineate potential mechanisms/factors influencing this.