CD19 CAR-T / Shanghai Yake Biotech - LARVOL DELTA

Prospective phase I/II study of CD19-directed CAR-t therapy in relapsed/refractory central nervous system lymphoma: Clinical outcomes and safety profile (ASH 2025) - "The therapeutic potential of CD19 CAR-T therapy for hematological malignancies wasdocumented in this analysis, especially for central nervous system lymphoma results in controllableadverse events and significantly improves the clinical treatment outcome."

Clinical • Clinical data • P1/2 data • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma

Rituximab, lenalidomide, and zanubrutinib (ZR2) with sequential CAR-T cell as first-line therapy for high-risk large B cell lymphoma (ASH 2025) - "Afterleukapheresis and lymphodepletion, these patients received sequential CD19 CAR-T cell infusion. This treatment is characterized by high CRrate, acceptable toxicity and great survival outcomes. This establishes the potential for developing CAR-Ttherapy as first-line therapy for LBCL."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

CD19/BCMA CAR-T Cell Therapy for Refractory Systemic Lupus Erythematosus - Safety and Preliminary Efficacy Data from a Phase I Clinical Study (ASH 2023) - "After lymphodepleting chemotherapy with cyclophosphamide/fludarabine (D-4 to D-2), patients receive a single infusion of 1-2x106 CD19 CAR-T cells and BCMA CAR-T cells per kilogram of body weight at D0...All patients had active severe SLE and had received glucocorticoids, hydroxychloroquine, tacrolimus, total glucosides of paeony, merti-macrolide, leflunomide, azathioprine, methotrexate, cyclophosphamide, immunoglobulin, rituximab, belimumab, and Tetracycline before treatment with CAR-T cells, which were standard treatments that were either ineffective or difficult to withdraw.3 patients received 1x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells, and 9 patients received 2x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells 2x10^6/kg... These data suggest that CD19/BCMA CAR-T cell therapy is well tolerated and can induce rapid and durable remission in severe refractory SLE."

CAR T-Cell Therapy • Clinical • P1 data • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • Systemic Lupus Erythematosus

A Multicenter Study of CAR-T Cells in Primary Ph+All (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Zhejiang University

New P2 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Dasatinib and CAR-T Cell Therapy for Newly Diagnosed Ph-Positive Acute Lymphoblastic Leukemia in Adults (ASH 2023) - "Dasatinib in combination with a two-week vincristine and glucocorticoids regimen were administered, followed by sequential infusions of CD19 and CD22 CAR-T cells...Results At the cut-off date of 31 May 2023, 18 patients have received CD19 CAR-T cell infusions, and 14 of these patients have received subsequent CD22 CAR-T cell infusions...Conclusions Dasatinib in combination with CAR-T cell therapy has enabled chemotherapy-free treatment in newly diagnosed Ph-positive ALL. This treatment is characterized by high complete molecular response, high long-term survival, low toxicity and short treatment cycles."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CD22

Sequential CD19 and CD22 CAR-T Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia (ASH 2024) - "Patients underwent CD19 CAR-T cell infusion followed by CD22 CAR-T cell infusion after at least one month. Of the 8 relapsed patients, loss of BCA preceding relapse was observed in 3 cases (37.5%), concurrent loss of BCA and relapse in 4 cases (50%), ongoing BCA in 1 case (12.5%). Conclusion : Sequential CD19 and CD22 CAR-T cell therapy demonstrates durable efficacy and a manageable safety profile in relapsed/refractory B-ALL, providing a promising option to address antigen-loss relapse and improve long-term outcomes in patients ineligible for allo-HSCT."

Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • CD22

Rituximab, Lenalidomide, and Zanubrutinib (ZR2) with Sequential CAR-T Cell As First-Line Therapy for High-Risk Large B Cell Lymphoma (ASH 2024) - "Patients received two cycles of ZR2 (rituximab 375 mg/m2 intravenous once on day 1, lenalidomide 25 mg once per day on days 1-21, and zanubrutinib 160 mg twice daily continuously of each 28-day cycle), and those with efficacy assessment of partial response or stable disease received sequential CD19 CAR-T cell therapy. Conclusions ZR2 with sequential CAR-T cell therapy has enabled chemo-free treatment in newly diagnosed high-risk LBCL. This treatment is characterized by high CR rate, high long-term survival, and low toxicity."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

Safety and efficacy of autologous humanized CD19 CAR-T cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma. (PubMed, Bone Marrow Transplant) - "CAR-T expansion was observed in all patients (median peak: 220.63 cells/µL). hCART19 demonstrated favorable efficacy and manageable toxicity in R/R B-NHL, providing critical clinical evidence for its clinical application."

Journal • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CAR-T TREATMENT STRATEGY FOR B-CELL LYMPHOMA: HIGH COMPLETE RESPONSE RATE IN M2 MACROPHAGES AND GRANULOCYTES DEFICIENCY IMMUE MICROENVIRONMENT (EHA 2025) - "This study aims to identify CD19 CAR-T sensitive immune cells by comparing complete response rate (CRR) of different immune cell groups after CAR-T treatment.The ROC curve threshold value with the highest sensitivity and specificity was used to group the B-cell lymphoma biopsy samples with different immune cells proportion... As a prognostic risk factor, M2 macrophages and granulocytes not only affect the overall survival of the patient, but also are closely related to the CRR of the patient. Our findings have important implications for the study of factors influencing CAR-T infiltration in B-cell lymphoma."

Clinical • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4

Dasatinib and CAR T-Cell Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "Dasatinib was administered with a 2-week vindesine and dexamethasone regimen as induction, followed by sequential CD19 and CD22 CAR T-cell therapies and single-agent dasatinib maintenance. The primary end point was CMR rate after CD19 CAR T-cell therapy...Further studies with larger cohorts and longer follow-up durations are needed. ClinicalTrials.gov Identifier: NCT04788472."

Clinical • Journal • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CD22

LONG-TERM FOLLOW-UP OF CAR-T THERAPY FOLLOWED BY HAPLOIDENTICAL HSCT FOR RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA: A MULTI-CENTER RETROSPECTIVE STUDY (EBMT 2025) - P=N/A | " We previously reported the results of 122 patients with r/r ALL received anti-CD19 CAR-T including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haplo-HSCT (transplant group) at a median follow-up of 20.4 months. Haploidentical hematopoietic stem cell transplantation with pre-transplant MRD negativity after CAR-T therapy could greatly improve LFS and OS in patients with relapsed/refractory acute lymphoblastic leukemia. However, infections are key survivorship issues that reduce long-term survival after CAR T-cell therapy. Clinical Trial Registry: The study was registered in the Chinese clinical trial registry (ChiCTR1900023957)."

Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Cardiovascular • Chronic Graft versus Host Disease • Congestive Heart Failure • Graft versus Host Disease • Heart Failure • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology

Donor Derived CD19 CAR-T Cells in the Treatment of R/R B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Zhejiang University

New P1 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

ZANUBRUTINIB ENHANCES CD19 CART KILLING OF B-CELL LYMPHOMA BY INHIBITING BTK PHOSPHORYLATION, REGULATING PI3K/AKT/MTOR PATHWAY AND PROMOTING AUTOPHAGY (EHA 2024) - "Collectively, Zanubrutinib enhances CD19 CART killing of B-cell lymphoma by inhibiting BTK phosphorylation,regulating PI3K/AKT/mTOR pathway and promoting autophagy. Figure 1"

IO biomarker • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BAX • BCL2 • CASP3 • PIK3CA

CD22-TARGETED IMMUNOTHERAPY FOR ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-ALL WHO PREVIOUSLY EXPOSED TO CD19-TARGETED IMMUNOTHERAPY (EBMT 2024) - "Six (20.0%) patients were exposed to blinatumomab only, 20 (66.7%) patients were exposed to CD19 CAR-T cell therapy only, and 4 (13.3%) patients were exposed to both. 20 (66.7%) patients received CD22 CAR-T cell therapy, and 10 (33.3%) patients received inotuzumab ozogamicin... CD22-targeted immunotherapy is an effective treatment option for patients with r/r B-ALL who previously exposed to CD19-targeted immunotherapy. However, the relapse rate post CD22-targeted immunotherapy remains high. Therefore, new strategies are still needed to improve the prognosis of this group of patients."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Infectious Disease • Transplantation • CD19 • CD22

CD22-TARGETED IMMUNOTHERAPY FOR ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-ALL WHO PREVIOUSLY EXPOSED TO CD19-TARGETED IMMUNOTHERAPY (EBMT 2024) - "Six (20.0%) patients were exposed to blinatumomab only, 20 (66.7%) patients were exposed to CD19 CAR-T cell therapy only, and 4 (13.3%) patients were exposed to both. 20 (66.7%) patients received CD22 CAR-T cell therapy, and 10 (33.3%) patients received inotuzumab ozogamicin... CD22-targeted immunotherapy is an effective treatment option for patients with r/r B-ALL who previously exposed to CD19-targeted immunotherapy. However, the relapse rate post CD22-targeted immunotherapy remains high. Therefore, new strategies are still needed to improve the prognosis of this group of patients."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Infectious Disease • Transplantation • CD19 • CD22

CD19 CAR-T Therapy for Patients With B-cell Non-Hodgkin's Lymphoma (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Zhejiang University | Not yet recruiting ➔ Recruiting | Phase classification: P1 ➔ P2 | Trial primary completion date: Dec 2023 ➔ Dec 2026

Enrollment open • Phase classification • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology