CD19 CAR T-cell therapy (GLPG5101) for relapsed or refractory B-cell non-Hodgkin lymphoma (ATALANTA-1): phase 1 results from a single-arm, multicentre, phase 1/2 study.

Effectiveness of anti-CD19 CAR T-cell therapy for high-grade B-cell lymphoma in Japan: a single-institution analysis.

Epcoritamab with rituximab and lenalidomide as first-line treatment for follicular lymphoma (EPCORE NHL-2): an open-label, multicentre, phase 1/2 b trial.

BACKGROUND Chemotherapy-free regimens, such as rituximab and lenalidomide, are attractive first-line treatment options for follicular lymphoma, but combinations providing deeper, more durable responses are needed. We aimed to assess 3-year activity and safety of epcoritamab, a subcutaneously administered CD3 × CD20 bispecific antibody, plus rituximab-lenalidomide as first-line treatment for follicular lymphoma. METHODS EPCORE NHL-2 is an open-label, phase 1b/2, clinical trial. Arm 6 of the study was conducted at 20 hospitals in six countries in Europe (Spain, the Netherlands, Czech Republic, Sweden, Belgium, and Denmark) and the USA in patients aged 18 years and older with CD20+, histologically confirmed grade 1-3A follicular lymphoma, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received intravenous rituximab 375 mg/m2 once per week in cycle 1 (28 days per cycle) and every 4 weeks in cycles 2-6; oral lenalidomide 20 mg daily on days 1-21 of cycles 1-12; and subcutaneous epcoritamab in a two-step-up dosing regimen of a 0·16 mg priming dose, followed by a 0·8 mg intermediate dose, then full 48 mg doses in cycle 1, 48 mg once per week in cycle 2, and 48 mg every 4 weeks in subsequent cycles for up to 2 years. The primary endpoint was investigator-assessed overall response rate by Lugano Response Criteria for Malignant Lymphoma. The full analysis set and the safety set included all patients who received one or more doses of trial drug. This study is registered with ClinicalTrials.gov (NCT04663347) and is ongoing (closed to new participants). FINDINGS Between Sept 23, 2021, and May 3, 2022, 45 patients were assessed for eligibility in Arm 6, 41 of whom were eligible and included in the full analysis and safety sets. 21 (51%) of 41 patients were male and 20 (49%) were female; 27 (66%) of patients were White, one (2%) was Asian, one (2%) was of another race, and 12 (29%) did not have race reported. At a median follow-up of 35·9 months (IQR 35·8-36·6) the overall response rate was 95% (95% CI 84-99; 39 of 41 patients). The most common grade 3-4 adverse events were neutropenia (20 [49%] of 41 patients), infections (12 [29%]), COVID-19 (six [15%]), and alanine aminotransferase increase (five [12%]). Serious adverse events occurred in 29 (71%) patients, including cytokine release syndrome (13 [32%]), serious infections (13 [32%]; one grade 2), pyrexia (three [7%]), organising pneumonia (one [2%]), pleural effusion (one [2%]), pneumonitis (one [2%]), pulmonary embolism (one [2%]), maculopapular rash (two [5%]), toxic skin eruption (one [2%]), atrial fibrillation (one [2%]), diarrhoea (one [2%]), dehydration (one [2%]), ovarian epithelial cancer (one [2%]), cerebrovascular accident (one [2%]), and thrombophlebitis (one [2%]). Treatment-related deaths occurred in three (7%) patients due to septic shock, progressive multifocal leukoencephalopathy, and COVID-19. INTERPRETATION Epcoritamab plus rituximab-lenalidomide showed high activity in first-line treatment for follicular lymphoma, with 95% of patients having a response over 3 years of follow-up, supporting this treatment regimen as a promising approach that warrants further analysis to ascertain its role in this setting. FUNDING Genmab and AbbVie.

Ultralow-Dose Interleukin 10-Expressing Chimeric Antigen Receptor T Cells in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Nonrandomized Clinical Trial.

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.

Bicistronic CD19/CD22 CAR T-Cell Therapy in Pediatric B-Cell Acute Lymphoblastic Leukemia: A Nonrandomized Clinical Trial.

Second Line CD19 CAR-T vs Platinum Salvage and Autologous Stem Cell Transplant for Primary Mediastinal B-Cell Lymphoma.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of large B-cell lymphoma (LBCL) with around 90% of patients cured with frontline treatment. For relapsed or refractory (R/R) disease, the optimal treatment is unclear. CD19 chimeric antigen receptor-T cell (CAR-T) has been established as the preferred second line (2L) treatment for primary refractory or early relapsing LBCL based on the overall survival benefits observed in the landmark phase III trials. However, PMBCL patients were underrepresented on these pivotal studies. This study evaluated outcomes of 252 patients treated with 2L therapies for R/R PMBCL at 14 US institutions between 2001 and 2025. Platinum-based salvage with intent to proceed to high dose therapy and autologous stem cell transplant (HDT/ASCT) (platinum cohort) and CD19 CAR-T (CAR-T cohort) were given as 2L therapy in the real-world setting in 157 and 26 patients, respectively. Overall response rate (ORR), complete response (CR) rate and median progression-free survival (PFS) were significantly higher in the CAR-T cohort compared with the platinum cohort (ORR: 91.3% vs 44.2%, p <0.001; CR 65.2% vs 14.7%, p<0.001; median PFS not reached vs 3.5 months, hazard ratio (HR) 0.28, 95% CI 0.15-0.54, p=0.001). No significant difference was observed in overall survival. This study demonstrated superior response rate and PFS of CD19 CAR-T over platinum-based salvage with intent to proceed to HDT/ASCT as 2L treatment for R/R PMBCL.

Academic anti CD19 CAR-T cell therapy for relapsed/refractory B-cell lymphomas in real-world clinical practice: a prospective cohort study

Background/objective Chimeric antigen receptor (CAR) T-cell therapy has been the standard of care for relapsed/refractory B-cell lymphomas (r/r BCLs) in recent years. However, high cost of commercial products limits their application in real-world clinical practice. The use of the so-called academic CAR-T cell products can reduce the cost and improve availability and affordability of this therapy option. The aim of the present clinical trial was to assess the efficacy and safety of academic CAR-T cells in r/r BCL patients. Materials and methods From June 2021 to December 2025, this prospective clinical trial enrolled 76 r/r BCL patients treated at the N.N. Alexandrov National Cancer Centre of Belarus (Minsk, Republic of Belarus), ClinicalTrials.gov Identifier: NCT07524816. The patients were 23–68 years of age (median 47 years). The CAR-T cell product was manufactured using lentiviral vector encoding anti-CD19 CAR. Results The median follow-up was 7.85 months for the entire cohort and 20.12 months for patients without events. Generally, complete response was achieved in 57.5% of patients. The 4-year event-free survival (EFS) rate was 46.2 ± 6.3%, and the 4-year overall survival (OS) rate was 67 ± 5.9%. Among patients with follicular lymphoma (FL), complete response was achieved in 83.3% patients. The 4-year EFS was 81.7 ± 9.6%. The safety profile was acceptable: cytokine release syndrome (CRS) was detected in 43.4% of patients (≥ grade 3 in 2.6%). No cases of grade 4 CRS were reported, and neurotoxicity (ICANS) was identified in 26.3% of patients (≥ grade 3 in 5.3%, grade 4 ICANS occurred in two patients – 2.6%). Conclusion The anti-CD19 CAR T-cell product demonstrates good efficacy and acceptable toxicity in patients with r/r BCL. The use of such a product is the only available option for patients in countries where commercial products are not accessible. Clinical trial registration https://clinicaltrials.gov/study/NCT07524816, identifier NCT07524816.