Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial

D'Angelo, Sandra P; Araujo, Dejka M; Abdul Razak, Albiruni R; Agulnik, Mark; Attia, Steven; Blay, Jean-Yves; Carrasco Garcia, Irene; Charlson, John A; Choy, Edwin; Demetri, George D; Druta, Mihaela; Forcade, Edouard; Ganjoo, Kristen N; Glod, John; Keedy, Vicki L; Le Cesne, Axel; Liebner, David A; Moreno, Victor; Pollack, Seth M; Schuetze, Scott M; Schwartz, Gary K; Strauss, Sandra J; Tap, William D; Thistlethwaite, Fiona; Valverde Morales, Claudia Maria; Wagner, Michael J; Wilky, Breelyn A; McAlpine, Cheryl; Hudson, Laura; Navenot, Jean-Marc; Wang, Tianjiao; Bai, Jane; Rafail, Stavros; Wang, Ruoxi; Sun, Amy; Fernandes, Lilliam; Van Winkle, Erin; Elefant, Erica; Lunt, Colin; Norry, Elliot; Williams, Dennis; Biswas, Swethajit; Van Tine, Brian A

doi:10.1016/s0140-6736(24)00319-2

Cited by 37 publications

(2 citation statements)

References 28 publications

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“… 15 , 16 Their clinical utility has been further confirmed in a phase 2 trial of afami-cel in SyS and MRCLS. 21 Thus, the MAGE-A4 prevalence reported here is of significance in guiding future clinical trial development for anti-MAGE-A4 TCR T cell therapies. In our samples, SyS showed the highest MAGE-A4 expression, whereas gastric cancer showed the lowest.…”

Section: Discussionmentioning

confidence: 78%

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Identifying MAGE-A4-positive tumors for TCR T cell therapies in HLA-A∗02-eligible patients

Wang,

Navenot,

Rafail

et al. 2024

Molecular Therapy - Methods & Clinical Development

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Section: Discussionmentioning

confidence: 78%

“…However, the overall response rate per RECIST 1.1 obtained in SyS and other indications demonstrates the clinical validity of the screening process. 15 , 16 , 21 …”

Section: Discussionmentioning

confidence: 99%

Identifying MAGE-A4-positive tumors for TCR T cell therapies in HLA-A∗02-eligible patients

Wang,

Navenot,

Rafail

et al. 2024

Molecular Therapy - Methods & Clinical Development

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CAR T Cells and T-Cell Therapies for Cancer

Brudno,

Maus,

Hinrichs

2024

JAMA

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ImportanceChimeric antigen receptor (CAR) T cells are T lymphocytes that are genetically engineered to express a synthetic receptor that recognizes a tumor cell surface antigen and causes the T cell to kill the tumor cell. CAR T treatments improve overall survival for patients with large B-cell lymphoma and progression-free survival for patients with multiple myeloma.ObservationsSix CAR T-cell products are approved by the US Food and Drug Administration (FDA) for 6 hematologic malignancies: B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma. Compared with standard chemotherapy followed by stem cell transplant, CAR T cells improved 4-year overall survival in patients with large B-cell lymphoma (54.6% vs 46.0%). Patients with pediatric acute lymphoblastic leukemia achieved durable remission after CAR T-cell therapy. At 3-year follow-up, 48% of patients were alive and relapse free. In people with multiple myeloma treated previously with 1 to 4 types of non–CAR T-cell therapy, CAR T-cell therapy prolonged treatment-free remissions compared with standard treatments (in 1 trial, CAR T-cell therapy was associated with progression-free survival of 13.3 months compared with 4.4 months with standard therapy). CAR T-cell therapy is associated with reversible acute toxicities, such as cytokine release syndrome in approximately 40% to 95% of patients, and neurologic disorders in approximately 15% to 65%. New CAR T-cell therapies in development aim to increase efficacy, decrease adverse effects, and treat other types of cancer. No CAR T-cell therapies are FDA approved for solid tumors, but recently, 2 other T lymphocyte–based treatments gained approvals: 1 for melanoma and 1 for synovial cell sarcoma. Additional cellular therapies have attained responses for certain solid tumors, including pediatric neuroblastoma, synovial cell sarcoma, melanoma, and human papillomavirus–associated cancers. A common adverse effect occurring with these T lymphocyte–based therapies is capillary leak syndrome, which is characterized by fluid retention, pulmonary edema, and kidney dysfunction.Conclusions and RelevanceCAR T-cell therapy is an FDA-approved therapy that has improved progression-free survival for multiple myeloma, improved overall survival for large B-cell lymphoma, and attained high rates of cancer remission for other hematologic malignancies such as acute lymphoblastic leukemia, follicular lymphoma, and mantle cell lymphoma. Recently approved T lymphocyte–based therapies demonstrated the potential for improved outcomes in solid tumor malignancies.

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Immunonkologie

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2024

Onkologie

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Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial

Cited by 37 publications

References 28 publications

Identifying MAGE-A4-positive tumors for TCR T cell therapies in HLA-A∗02-eligible patients

Identifying MAGE-A4-positive tumors for TCR T cell therapies in HLA-A∗02-eligible patients

CAR T Cells and T-Cell Therapies for Cancer

Immunonkologie

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