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Durable control of metastases in an HLA-A2+ patient with refractory melanoma after low-dose radiotherapy in combination with MAGE-A4 T cell therapy: a case report

Authors :
He, Kewen
Hong, David S.
Ke, Danxia
Kebriaei, Partow
Wang, Tianjiao
Danesi, Hassan
Bertolet, Genevieve
Leuschner, Carola
Puebla-Osorio, Nahum
Voss, Tiffany A.
Lin, Quan
Norry, Elliot
Fracasso, Paula M.
Welsh, James W.
Source :
Melanoma Research; August 2023, Vol. 33 Issue: 4 p332-337, 6p
Publication Year :
2023

Abstract

There is no currently approved adoptive cellular therapy for solid tumors. Pre-clinical and clinical studies have demonstrated that low-dose radiotherapy (LDRT) can enhance intratumoral T cell infiltration and efficacy. This case report describes a 71-year-old female patient with rectal mucosal melanoma that had developed metastases to liver, lung, mediastinum, axillary nodes, and brain. After systemic therapies had failed, she enrolled in the radiation sub-study of our phase-I clinical trial exploring the safety and efficacy of afamitresgene autoleucel (afami-cel), genetically engineered T cells with a T cell receptor (TCR) targeting the MAGE-A4 tumor antigen in patients with advanced malignancies (NCT03132922). Prior to the infusion of afami-cel, she received concurrent lymphodepleting chemotherapy and LDRT at 5.6 Gy/4 fractions to the liver. Time to partial response was 10 weeks, and duration of overall response was 18.4 weeks. Although the patient progressed at 28 weeks, the disease was well controlled after high-dose radiotherapy to liver metastases and checkpoint inhibitors. As of the last follow-up, she remains alive over two years after LDRT and afami-cel therapy. This report suggests that afami-cel in combination with LDRT safely enhanced clinical benefit. This provides evidence for further exploring the benefit of LDRT in TCR-T cell therapy.

Details

Language :
English
ISSN :
09608931 and 14735636
Volume :
33
Issue :
4
Database :
Supplemental Index
Journal :
Melanoma Research
Publication Type :
Periodical
Accession number :
ejs63448596
Full Text :
https://doi.org/10.1097/CMR.0000000000000869