Abstract
We report on 12 consecutive patients with advanced/metastatic Ewing's sarcoma who were treated as a separate cohort of a phase 1 trial of FANG autologous immunotherapy (1 × 106–2.5 × 107 cells/intradermal injection each month for minimum 4 months). Safety and clinical response were monitored. Patient immune response to unmodified autologous tumor cells was assessed by gamma interferon-enzyme-linked immunospot (γIFN-ELISPOT) assay using peripheral blood mononuclear cells from baseline (pretreatment) and multiple postvaccination time points. None of the 12 patients (47 vaccinations) developed grade 2/3/4 drug-related toxicity. Median product release granulocyte-macrophage colony-stimulating factor expression was 1,941 pg/106 cells, and TGFβ1and TGFβ2 knockdown were 99 and 100%, respectively. Eight patients were assessed for ELISPOT response to autologous tumor cells at baseline and all (100%) were negative. In contrast, follow-up ELISPOT response at month 1 or month 4 (one patient) after FANG was positive in all eight patients. One patient achieved a partial tumor response (38% tumor reduction, RECIST 1.1). The Kaplan–Meier estimated survival of these 12 patients at 1 year was 75%. In this phase 1 study in patients with Ewing's sarcoma, FANG immunotherapy was well tolerated, elicited a tumor-specific systemic immune response in all patients, and was associated with favorable 1-year survival. Further clinical testing is indicated.
Highlights
Ewing’s sarcoma (EWS) is a rare adolescent malignant bone tumor distinguished by a translocation of the EWS gene on chromosome 22q12 with one of the E26 transformation-specific transcription factory family genes.[1]
We report on 12 consecutive patients with advanced/ metastatic Ewing’s sarcoma who were treated as a separate cohort of a phase 1 trial of FANG autologous immunotherapy (1 × 106–2.5 × 107 cells/intradermal injection each month for minimum 4 months)
Few EWS patients respond to second-line therapy and there is no standard of care second-line treatment
Summary
Ewing’s sarcoma (EWS) is a rare adolescent malignant bone tumor distinguished by a translocation of the EWS gene on chromosome 22q12 with one of the E26 transformation-specific transcription factory family genes.[1] Up to 85% of Ewing’s tumors are characterized by the (11;22)(q24;12) translocation resulting in the EWS/FLI1 fusion gene.[2] The median age of diagnosis for adolescents with EWS is 14 years.[3,4] The 5-year survival with standard of care is ~30% for EWS patients with metastatic lesions isolated to the lung and
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