The initial results indicate that CD7 CAR-T cell therapy exhibits a manageable safety profile and preliminary efficacy in R/R AML patients, supporting further investigation in larger trials.
The TRAVERSE trial demonstrates proof of concept for the role of allogeneic CAR T-cell therapy in solid tumors and had manageable safety and encouraging antitumor activity in CD70-positive ccRCC.
S. Srour, J. Chahoud, A. Drakaki et al.· Journal of Clinical Oncology· 0 citations
Background Relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) has poor outcomes and limited salvage options. Objectives: To evaluate the efficacy and safety of daratumumab-based therapy in R/R T-ALL/T-LBL. Design Systematic review of observational reports. Methods Sixteen reports including 34 patients treated with daratumumab-based regimens were reviewed. Baseline characteristics, treatment patterns, response, MRD status, survival, allogeneic HSCT, and safety were descriptively synthesized. Results Complete remission was reported in 30/34 patients (88.2%), partial remission in 2/34 (5.9%), and no response in 2/34 (5.9%). Among complete responders with reported MRD status, 24/29 (82.8%) achieved MRD negativity. Median PFS was 10 months (range, 0.4–45), and median OS was 10 months (range, 1.5–45), although many values reflected last follow-up. Eighteen patients (52.9%) proceeded to allogeneic HSCT; 13/18 (72.2%) were alive at last follow-up. Infusion reactions occurred in 10 patients, mostly grade 1–2. Conclusion Daratumumab-based therapy may induce remission and facilitate HSCT bridging in selected patients, but findings remain hypothesis-generating because evidence is mainly from case reports and small series.
A. Al-Mashdali, Mujahid O. Abdelraof, Monia Ibrahim et al.· Therapeutic Advances in Hema...· 0 citations
CD19-directed therapy remains the mainstay treatment for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). However, treatment patterns and outcomes following CD19-negative (CD19-) relapse remain poorly defined. We retrospectively analyzed 65 adult patients with ALL who developed CD19-relapse after CD19-directed therapy. TP53 mutations and BCR::ABL1-like ALL were each identified in 27.7% (n = 18) of patients. Forty-six patients (70.8%) received one CD19-targeted therapy, whereas 19 patients (29.2%) received ≥ 2 prior to CD19-relapse. Overall, 60 patients (92.3%) received blinatumomab, and 23 (35.4%) received CAR T-cell therapy. The median time from the initiation of the most recent CD19-targeted therapy to CD19-relapse was 155 days (range, 13-1946). The median follow-up of the entire cohort was 32.7 months (IQR, 15.1-90.3). The median event-free and overall survival (EFS and OS) was 3.1 months (95% CI, 2.5-4.5) and 9.9 months (95% CI, 6.8-24.7), respectively. In multivariate analysis, receipt of ≥ 2 CD19-directed therapies was associated with both inferior EFS and OS, HR 2.17 (95% CI, 1.10-4.29; p = 0.03) and HR 3.05 (95% CI, 1.40-6.62; p = 0.005). The complete remission rate following first salvage therapy was 47.5% and 72.1% any time following CD19-relapse. Sixteen (34.8%) of 46 patients evaluated had subsequent CD19 re-expression, 5 of whom subsequently received CD19-directed therapy, and all 5 patients responded. Patients with ALL who develop CD19-relapse after CD19-directed therapy have poor outcomes and limited therapeutic options. However, since this study lacked a comparator cohort of patients with CD19-positive relapse, the independent prognostic impact of CD19 negativity could not be determined.
T. Othman, Vaibhav Agrawal, Joo Y. Song et al.· American journal of hematolo...· 0 citations
Importance
Interleukin (IL)-10 expressing CD19 chimeric antigen receptor (CAR) T cells (META 10-19) have demonstrated encouraging clinical activity in B-cell acute lymphoblastic leukemia, but their safety and efficacy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remain unknown.
Objective
To evaluate the safety and efficacy of META 10-19 in patients with R/R DLBCL.
Design, Setting, and Participants
This nonrandomized, phase 1 clinical trial was conducted at the First Affiliated Hospital of Zhejiang University School of Medicine. Patients were enrolled from November 16, 2023, to April 7, 2025. The data cutoff date was January 20, 2026. The data analysis was conducted on January 22, 2026. Twenty patients were screened, and 13 received a META 10-19 infusion. The median duration of follow-up was 15.6 (range, 0.7-25.5) months.
Intervention
Following lymphodepletion with fludarabine and cyclophosphamide, patients received META 10-19 at dose levels of 2 × 103, 5 × 103 or 2 × 104 CAR T cells/kg.
Main Outcomes and Measures
The primary end points were adverse events, dose-limiting toxic effects, and objective response rate. The secondary end points included complete remission (CR) and a cellular kinetic of META 10-19.
Results
Among 13 treated patients (median age, 61 years [range, 35-74 years]; 8 men [61.5%] and 5 women [38.5%]), the objective response rate was 92.3%, including CR in 11 patients (84.6%) and partial remission in 1 patient (7.7%). One patient died before response assessment because of disease-related gastrointestinal complications. Cytokine release syndrome occurred for 12 patients (grade 1: n = 8; grade 2: n = 3; grade 3: n = 1), and immune effector cell-associated neurotoxicity syndrome occurred for 2 patients (grade 1: n = 1; grade 2: n = 1). Robust in vivo CAR T-cell expansion was observed across dose levels, with a median (range) peak expansion of 660.7 (30.7-10 562.3) cells/µL. At data cutoff, 5 patients experienced a maintained CR and 7 experienced disease relapses or progression (2 with CD19 negative relapses).
Conclusions and Relevance
The results of this nonrandomized clinical trial suggest that ultralow-dose META 10-19 demonstrated promising antitumor activity and a manageable safety profile in patients with R/R DLBCL. Further investigation in larger cohorts is warranted.
Trial Registration
ClinicalTrials.gov Identifier: NCT06120166.
Yong-xian Hu, Mingming Zhang, M. Gao et al.· JAMA Oncology· 0 citations
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with poor prognosis. Current Immunotherapies, including chimeric antigen receptor (CAR) T cell strategies, are limited by the scarcity of antigens that are present on AML cells but absent from hematopoietic stem and progenitor cells (HSPCs). To identify a potential therapeutic target, we analyzed two publicly available single-cell RNA sequencing datasets and found that CD4 is frequently expressed on AML blasts but absent from HSPCs, supporting its potential as a novel CAR target. We developed a CD4-targeted CAR using CD3+CD4⁻CD8⁻ double-negative T cells (CAR4-DNTs). DNTs offer a unique therapeutic platform: they naturally lack CD4, preventing fratricide, and elicit endogenous anti-leukemic activity. Their feasibility and safety as an allogeneic cell therapy platform was demonstrated in a Phase I trial. This work aims to establish CAR4-DNTs as a next-generation, off-the-shelf CAR-T cell therapy for AML.
Donor-derived DNTs were engineered to express a CD4-CAR. Cytotoxicity, persistence, and cytokine secretion were evaluated against AML cell lines, CD4+ and CD4-knockout AML variants, and primary AML samples. NSG-SGM3 mice engrafted with luciferase+ MV4-11 cells received CAR4-DNTs, untransduced (UT) DNTs, or PBS. Disease progression was monitored by bioluminescence imaging and survival analysis.
CAR4-DNTs were successfully manufactured without fratricide. They exhibited significantly enhanced and more durable cytotoxicity than UT-DNTs against AML cell lines and patient samples. Importantly, CAR4-DNTs retained endogenous cytotoxicity towards CD4-negative AML cells. In vivo, CAR4-DNT achieved durable leukemia clearance and prolonged survival, whereas PBS-treated mice rapidly progressed and UT-DNT recipients showed transient disease control before relapse.
These findings establish CAR4-DNTs as a promising immunotherapy candidate for AML, supporting their further preclinical and translational development.
Distinguished Doctoral Recruitment Scholarship, The C17 Council, Alberta Cancer Foundation, Alberta Children’s Hospital Research Institute
Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
Shanshan Wang, Michele Nawata, Juan Arteaga et al.· Journal of Immunology· 0 citations
Background Persistent cytopenia following chimeric antigen receptor T-cell (CAR-T) therapy is an increasingly recognized complication in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). While most cases stem from transient, immune-mediated mechanisms or depleted bone marrow reserves, secondary therapy-related myeloid neoplasms (t-MN) must be strongly suspected in patients presenting with prolonged, transfusion-refractory cytopenias. Case presentation We report the case of a 76-year-old woman diagnosed with refractory DLBCL (non-germinal center B-cell subtype, stage IIIA, International Prognostic Index score of 4). Following multiple lines of chemo-immunotherapy (R-CDOP, R-CDOPE, R-ICE, local radiotherapy, and one cycle of Pola-R-ICE) and subsequent autologous CAR-T cell infusion, the patient developed persistent pancytopenia, characterized by severe, transfusion-refractory thrombocytopenia. A comprehensive bone marrow evaluation performed in February 2026 revealed multilineage dysplasia, 13% blasts, TP53 deletion/mutation, and a complex karyotype, establishing a diagnosis of therapy-related myelodysplastic syndrome with low blasts (t-MDS-LB). Within two months, the disease rapidly progressed to acute myeloid leukemia (t-AML) with 35% abnormal myeloid blasts. Combination therapy with azacitidine and venetoclax was initiated but discontinued due to profound myelosuppression and severe infection. Conclusion This case underscores that persistent post-CAR-T cytopenia can serve as an early manifestation of an underlying t-MN rather than transient hematotoxicity. Prompt and comprehensive bone marrow assessments—incorporating morphology, flow cytometry, cytogenetics, and molecular profiling—are paramount for patients with extensive prior exposure to cytotoxic regimens to avoid catastrophic diagnostic delays.
Longmei Chen, Wanchao Liu· Frontiers in Oncology· 0 citations