CD7-targeted CAR T-cell therapy, WU-CART-007, demonstrates encouraging anti-leukemic activity and a manageable safety profile in heavily pretreated patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL). This updated analysis from the phase II portion of a first-in-human, multicenter, phase I/II study evaluated the efficacy of a single WU-CART-007 infusion (900 million cells) following lymphodepleting chemotherapy in 13 patients (median age 23 years, range 14-47; median of five prior therapies; 46% with prior alloHCT). Baseline disease burden included extramedullary disease (EMD) in 38.4% of patients and 61.5% with bone marrow (BM) disease with median BM blasts of 82.5%.
Response was assessed via day 28 BM evaluation and PET-CT, where applicable. Composite complete remission (CRc), encompassing CR (BM blasts <5%, ANC ≥1000/μL, platelets ≥100,000/μL) and CR with incomplete recovery (CRi), defined by SUV uptake below liver/mediastinum in EMD, was evaluated. Objective response rate (ORR), comprising CRc and partial response (PR; reduced EMD uptake), and duration of response (DOR) from initial response to relapse/death were also assessed.
Of the 11 evaluable patients, the ORR was 91% (n=9), with a CRc rate of 73% (n=8; 6 CR, 2 CRi). Of the six CRc patients with measurable residual disease (MRD) data, 83% (n=5) achieved MRD negativity. Five patients proceeded to alloHCT. At a median follow-up of up to 9.9 months, median DOR was not reached, with four patients remaining in continuous CR at 9.1, 8.2, 6.7, and 6.7 months. In the five patients with EMD, the ORR was 80% (n=4; 2 CR, 2 PR), with PR demonstrating a 78.5% and 95.7% reduction in disease burden by Lugano criteria.
Given the scarcity of effective treatments for relapsed/refractory T-ALL/LBL, the researchers were encouraged to see WU-CART-007 induce strong responses with acceptable toxicity, enabling a number of heavily pretreated patients to proceed to potentially curative allogeneic stem cell transplantation. The observed response rates and favourable safety profile support the continued clinical development of WU-CART-007 as a potential therapeutic strategy in this high-need patient population. These data warrant further investigation in larger, confirmatory trials, including evaluation in MRD-positive patients and younger children.
References
- Aldoss I, Ghobadi A, Maude SL, et al. WU-CART-007, an allogeneic CAR T-cell targeting CD7 in relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL): phase 2 results. Abstract 207. Presented at the 2025 Tandem Meetings of ASTCT and CIBMTR; February 12-15, 2025; Honolulu, Hawaii.
- ASH Clinical News. CAR-T Shows Acceptable Efficacy, Safety in Phase II R/R T-ALL/LBL Study. Available at: https://ashpublications.org/ashclinicalnews/news/8460/car-t-shows-acceptable-efficacy-safety-in-phase-ii (Date last accessed: 19 February 2025)
Disclosure: This article was created by the touchHAEMATOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
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