Letetresgene autoleucel in advanced/metastatic myxoid/round cell liposarcoma Journal Article
| Authors: | D'Angelo, S. P.; Druta, M.; Van Tine, B. A.; Liebner, D.; Schuetze, S. M.; Tap, W. D.; Preston, J.; Goodison, S.; D'Souza, J. W.; Kapoor, G. S.; Suchindran, S.; Zajic, S.; Bhaskar, A.; Kaczynski, H.; Kim, J.; Klohe, E.; Corigliano, E.; Eleftheriadou, I.; Nathenson, M. J.; Somaiah, N. |
| Article Title: | Letetresgene autoleucel in advanced/metastatic myxoid/round cell liposarcoma |
| Abstract: | PURPOSEThe cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target in myxoid/round cell liposarcoma (MRCLS).METHODSIn this pilot study, we assessed the adoptive T-cell therapy NY-ESO-1c259T letetresgene autoleucel (lete-cel) in patients with human leukocyte antigen (HLA)-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-positive advanced/metastatic NY-ESO-1-expressing MRCLS. Patients underwent a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR). The primary end point was investigator-assessed overall response rate (ORR). Safety was assessed through adverse event (AE) reports. Correlative biomarker analyses were performed post hoc. The trial is registered at ClinicalTrials.gov (identifier: NCT02992743).RESULTSOf 23 enrolled patients, 10 in cohort 1 and 10 in cohort 2 received lete-cel. Investigator-assessed ORR was 20% (95% CI, 2.5 to 55.6) and 40% (95% CI, 12.2 to 73.8), median duration of response was 5.3 months (95% CI, 1.9 to 8.7) and 7.5 months (95% CI, 6.0 to not estimable [NE]), and median progression-free survival was 5.4 months (95% CI, 2.0 to 11.5) and 8.7 months (95% CI, 0.9 to NE) in cohorts 1 and 2, respectively. AEs included cytokine release syndrome and cytopenias, consistent with T-cell therapy/LDR. Post hoc correlative biomarkers showed T-cell expansion and persistence in both cohorts.CONCLUSIONTo our knowledge, this study is the first demonstrating the clinical promise of lete-cel in HLA-/NY-ESO-1-positive patients with advanced MRCLS. © 2025 American Society of Clinical Oncology. |
| Keywords: | adult; aged; middle aged; membrane proteins; pathology; tumor antigen; immunology; antigens, neoplasm; pilot study; pilot projects; ctag1b protein, human; membrane protein; therapy; adoptive immunotherapy; immunotherapy, adoptive; myxosarcoma; adverse event; procedures; liposarcoma, myxoid; humans; human; male; female |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 43 |
| Issue: | 15 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-05-20 |
| Start Page: | 1777 |
| End Page: | 1788 |
| Language: | English |
| DOI: | 10.1200/jco-24-01466 |
| PUBMED: | 39836945 |
| PROVIDER: | scopus |
| PMCID: | PMC12084024 |
| DOI/URL: | |
| Notes: | Article -- MSK corresponding author is Sandra D’Angelo -- Source: Scopus |
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