CD19 CAR-T / Shanghai Yake Biotech - LARVOL DELTA

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

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

GLOFITAMAB DEMONSTRATES SUPERIOR EFFICACY COMPARED WITH SECOND-DIFFERENT-TARGET CAR-T AS SALVAGE THERAPY AFTER CD19 CAR-T FAILURE IN R/R B-CELL NON-HODGKIN LYMPHOMA (EHA 2026) - "Characteristic Second-different-target CAR-T Salvage therapyn=77 (A group BsAb (CD3-CD20) Salvage therapyn=19) (B group Age Median(min:mas) 51(20-82) 55(26-68) Age>60y 25(32.5%) 4(21.1%) Sex,male 39(50.6%) 15(78.9%) ECOG 0-1 51(66.2%) 16(84.2%) ≥2 26(33.8%) 3(15.8%) Ann Arbor stage Ⅰ - Ⅱ 5(6.5%) 2(10.5%) Ⅲ - Ⅳ 72(93.5%) 17(89.5%) IPI 0-1 16(20.8%) 5(26.3%) 2 14(18.2%) 2(10.5%) 3 28(36.4%) 8(42.1%) 4-5 19(24.7%) 4(21.1%) Histology DLBCL 57(74.0%) 13(68.4%) FL/tFL 4(5.2%) 3(15.8%) BL 5(6.5%) 1(5.3%) SCNSL 5(6.5%) 2(10.5%) MCL 3(3.9%) PMBL 2(2.6%) Richter 1(1.3%) Best response after CD19 CART CR 16(20.8%) 6(31.6%) PR 22(28.6%) 2(10.5%) SD 11(14.3%) PD 27(35.1%) 11(57.9%) Not evaluated 1(1.3%) Failure post-CD19 CART Early failure(<6 months) 61(79.2%) 9(47.4%) Late failure(≥6 months) 16(20.8%) 10(52.6%) The median time from CD19 CART treatment to PD 2.8mrange:0.46~21.27m 4.9mrange0.5~38.2m Other Targets CART CD20 CART 58(75.3%) CD22 CART 15(19.5%) CD79b CART 3(3.9%)..."

CAR T-Cell Therapy • Clinical • B Cell Non-Hodgkin Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Secondary Central Nervous System Lymphoma • CD22 • CD70 • CD79B

EFFICACY OF CAR-T CELL THERAPY IN DOUBLE-EXPRESSOR TP53-POSITIVE RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: A MULTICENTER REAL-WORLD STUDY (EHA 2026) - "Fifty-one patients received CAR-T therapy alone (CD19: n=28; CD19/CD22: n=22; CD20/CD22: n=1), and two patients received autologous hematopoietic stem cell transplantation combined with CD19 CAR-T therapy...(B) Progression-free survival. Tick marks represent censored cases."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • CD20 • CD22 • TP53

CD19/BCMA-Targeted Chimeric Antigen Receptor-T Cell Therapy for Anti-HLA Antibody Sensitisation in Patients With Acute Leukaemia: A Pilot Clinical Study. (PubMed, HLA) - "Among them, one patient was treated with BCMA CAR-T cells, while six received CD19 CAR-T cells. This pilot study illustrates the potential safety and efficacy of CD19 and BCMA CAR-T cells in desensitising anti-HLA antibodies in patients with AML or B-ALL. However, only one patient received BCMA CAR-T cells in our cohort, so further research with an expanded sample size is essential for comprehensively evaluating the safety and efficacy of CD19/BCMA CAR-T cell therapy for anti-HLA antibody sensitisation."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Inflammation • Leukemia • Oncology • Transplantation

Pre-Transplant MRD Negativity and Age Under 40 Predict Superior Long-Term Survival in Relapsed/Refractory B-ALL After CAR-T Therapy Bridging to Haploidentical HSCT: A Multicenter Retrospective Study With 6-Year Follow-Up. (PubMed, Am J Hematol) - P=N/A | "We previously reported the results of 122 patients with R/R B-ALL who achieved minimal residual disease negative (MRD-) complete remission (CR) after anti-CD19 CAR-T, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haplo-HSCT (transplant group). However, infections emerged as a significant complication that may reduce the long-term survival benefits. Trial Registration: ClinicalTrials.gov identifier: ChiCTR1900023957."

Journal • Minimal residual disease • Retrospective data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Transplantation

CD22-targeted immunotherapy for B-cell acute lymphoblastic leukemia progressing following CD19-targeted immunotherapy. (PubMed, NPJ Precis Oncol) - "CD22-targeted therapies, including CD22 CAR-T cells and Inotuzumab Ozogamicin, show promise as alternatives, although data in those patients is limited...Among these patients, 27.9% received blinatumomab, 58.1% received CD19 CAR-T cells, and 14% received both...Patients with extramedullary disease had worse remission rates, and those previously resistant to CD19-targeted therapy had shorter RFS. CD22-targeted therapies offer a potential option for patients progressing after CD19-targeted immunotherapy, but high relapse rates highlight the need for better strategies for lasting remission."

IO biomarker • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD19 • CD22

Zanubrutinib enhances CD19 CAR T killing of B-cell lymphoma by inhibiting BTK phosphorylation, regulating PI3K/AKT/mTOR pathway, and promoting autophagy. (PubMed, Blood Sci) - "B-cell lymphoma cells Daudi were proportionally co-cultured with CD19 CAR T and intervened using different concentrations of zanubrutinib, and the changes of cell viability, apoptosis, autophagy, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway-related factors were assessed using the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Western blotting, transmission electron microscopy, and immunofluorescence staining. The results showed that zanubrutinib increased the sensitivity of B-cell lymphoma to CD19 CAR T-cells, promoted apoptosis and autophagy, and inhibited BTK phosphorylation and the PI3K/AKT/mTOR signaling pathway. Zanubrutinib can promote the killing of B-cell lymphoma by CD19 CAR T. Collectively, zanubrutinib enhances CD19 CAR T killing of B-cell lymphoma by inhibiting BTK phosphorylation, regulating PI3K/AKT/mTOR pathway, and promoting autophagy."

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

CD19 CAR T-Cell Therapy for Autoimmune Hemolytic Anemia. (PubMed, N Engl J Med) - P1 | "CD19 CAR T-cell therapy had expected toxic effects and resulted in sustained remission in patients with multirefractory AIHA. (Funded by the National Key Research and Development Program of China and others; ClinicalTrials.gov number, NCT06231368.)."

Journal • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Infectious Disease • Inflammation • CD4 • HLA-DRB5

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

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

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