Blincyto (blinatumomab) / Astellas, Amgen, BeOne Medicines - LARVOL DELTA

SAFETY AND EFFICACY OF T CELL ENGAGER THERAPY IN PATIENTS WITH REFRACTORY AUTOIMMUNE DISEASE (EULAR 2025) - "14 patients with rheumatoid arthritis (RA) were treated with the CD19xCD3 TCE blinatumomab, while 10 patients (systemic sclerosis (SSc), N=3, idiopathic inflammatory myositis (IIM) N=2, IgG4-related disease (IgG4-RD) N=2, primary Sjoegren's-Syndrome (SjS) N=1, Graves disease (GD) N=1,) and RA N=1) were treated with the plasma cells targeting BCMAxCD3 TCE teclistamab. Together, these results substantiate the feasibility of TCE treatment of to autoimmune disease. Most notable adverse events are low grade cytokine release syndrome and infections. Short term efficacy is high even in a refractory patient population, however relapses occur."

Clinical • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Grave’s Disease • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Myositis • Nephrology • Rheumatoid Arthritis • Rheumatology • Scleroderma • Sjogren's Syndrome • Systemic Lupus Erythematosus • Systemic Sclerosis • IFIH1

KT501, A CD19, BCMA-DIRECTED T-CELL ENGAGER (TCE), LEADS TO DEEP B-CELL DEPLETION AND MINIMAL CYTOKINE RELEASE IN VIVO (EULAR 2025) - "Background: B cell depletion therapies targeting CD19 or BCMA, including Chimeric antigen receptor T-cell (CAR-T) therapies and Bispecific antibody such as blinatumomab and Teclistamab, had shown impressive efficacy in treating B cell malignancy. Those preclinical data strongly support clinical development of KT501 in autoimmune disease treatment, which is expected to move into Phase I trial in Q4, 2025. [2] Bucci L, etal. Bispecific T cell engager therapy for refractory rheumatoid arthritis."

Preclinical • Immunology • Inflammatory Arthritis • Lupus • Oncology • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

Applications for SLE patient-derived PBMC-induced mouse model in preclinical pharmacological studies (EULAR 2025) - "In case 2, the T cell engager under test and positive control, Blincyto, were administered intravenously 7 days after PBMC inoculation, twice a week for three consecutive weeks... SLE patient-derived PBMC-induced mouse model exhibits similar pathological features seen in SLE patients such as high levels of autoantibodies and pathogenic B cells. It demonstrates good responses to B-cell directed therapeutic antibodies and cell therapies in pharmacological studies and offers a clinically relevant animal model to accelerate the development of novel therapies . [2] Chen J, et al."

Preclinical • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD20

The use of the CD3/CD19 T cell engager blinatumomab in severe systemic sclerosis : a case series (EULAR 2025) - "The treatment protocol included premedication with hydrocortisone (100 mg), paracetamol (1 g), and dexchlorpheniramine (5 mg), followed by continuous intravenous infusion of blinatumomab at 9 µg/day for 7 days, then 28 µg/day for another 7 days. This real-world study indicates that blinatumomab is safe for use in systemic sclerosis and may lead to clinically significant improvements, including benefits for skin and lung manifestations. Biological impact of blinatumomab treatment (Patient 1). (A) Peripheral CD19+ B cells, (B) total immunoglobulin levels, and (C) post-vaccination serologies."

Clinical • Cardiovascular • Fatigue • Fibrosis • Immunology • Infectious Disease • Inflammation • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Treatment of severe systemic sclerosis with blinatumomab, a bispecific anti-CD3/CD19 T cell engager (EULAR 2025) - "We present the first cases worldwide in which blinatumomab was used as a B-cell-depleting therapy in a non-malignant disease. Blinatumomab was safe with transient neutropenia in one of the three patients and resulted in profound B-cell depletion and a significant decrease in serum IgG. Remarkably, this did not lead to increased susceptibility to infections."

Cardiovascular • Fibrosis • Immunology • Infectious Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Neutropenia • Orthopedics • Pain • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

CC312, a CD19-targeting, co-stimulatory CD28 receptor-activating tri-specific T cell engager, for the treatment of autoimmune diseases (EULAR 2025) - "Certain BCDT monoclonal antibodies, e.g. rituximab, are also approved to treat several autoimmune diseases [1], however demonstrate poor B cells depletion in deep tissue which may limit the long-term disease control or remission in patients. CC312's capacity to induce more complete T cell activation and longer T cell durability of response as well as more potently and thoroughly eliminate pathogenic B cells versus leading bispecific TCE Blincyto has been demonstrated in both ex vivo and in vivo studies. This highlights the importance of CD28 co-stimulation and indicates strong potential benefit of CC312 in achieving the depth of response needed to effectively treat B cell-related autoimmune diseases in the clinical setting. [2] Fabian Müller, et al."

Trispecific • Immunology • Inflammatory Arthritis • Oncology • CD20 • CD4 • CD8

Induction of GC-free remission by the bispecific CD19xCD3 T cell engager blinatumomab in patients with severe, therapy-refractory anti-synthetase syndrome (EULAR 2025) - "All patients were anti-Jo1 antibody positive and were not responding to multiple immunosuppressive therapies including prednisone, immunoglobulins, rituximab. Treatment with blinatumomab induced rapid, glucocorticoid-free remission of myositis in all patients and improvement of all other manifestations. Blinatumomab may thus offer potential for induction of remission in treatment-refractory ASyS patients."

Clinical • Cardiovascular • Immunology • Infectious Disease • Inflammation • Myositis • Pulmonary Disease • Rare Diseases • Respiratory Diseases • CD20

Effects of the Anti-CD3/CD19 T-Cell Engager Blinatumomab in Severe Systemic Sclerosis (EULAR 2025) - "Blinatumomab effectively depletes B cell subsets and induces subtle changes in T cell activation and differentiation in SSc. The observed immune modulation aligns with clinical improvements, highlighting its potential therapeutic impact. Further studies will validate and expand these findings in larger cohorts."

IO biomarker • Fibrosis • Immune Modulation • Immunology • Scleroderma • Systemic Sclerosis • CCR7 • CD4 • CD8 • GZMA • GZMB • ICOS • IL7R • TCF7

Effects of T cell engagers treatment on B and T cells in autoimmune disease (EULAR 2025) - " 14 patients with RA were treated in our department with the TCE CD19xCD3 Blinatumomab, 10 patients with various autoimmune diseases including SSc, IIM, IgG4-RD and GD were treated with the plasma cell-targeting TCE BCMAxCD3 teclistamab...In three patients, B cells were already peripherally depleted because of previous rituximab therapy (mean 3.3 months before blinatumomab [range: 3–4])... Together, these data demonstrate the impact of TCEs on B cell depletion and reconstitution kinetics in AIDs. Furthermore, strong effects on the T cell compartment are observed, raising the intriguing possibility that their mechanism of action is not limited to the B cell depletion alone. [2] Hagen, M. et al."

IO biomarker • Grave’s Disease • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Myositis • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis • CD20 • CD27 • CD8 • PD-1

Navigating B-ALL in the Era of Blinatumomab. (PubMed, Am Soc Clin Oncol Educ Book) - "Looking forward, research is focusing on optimizing the use of blinatumomab, including its integration into reduced-intensity or chemotherapy-free regimens, alternative dosing schedules, and subcutaneous administration. As clinical use expands, emphasis must shift toward developing equitable, patient-centered delivery strategies and understanding the full spectrum of toxicities to ensure optimal and accessible care for all patients with B-ALL."

Journal • Review • Inflammation • Pediatrics • KMT2A

Treatment patterns and out-of-pocket cost after CAR-T cell therapy in commercially insured patients with hematologic malignancies: A real-world US study. (ASCO 2025) - "After CAR-T failure, the most common first-line therapies were lenalidomide (n=12), ibrutinib (n=7), and pembrolizumab (n=5) for DLBCL, and blinatumomab (n=3) and ruxolitinib (n=2) for ALL. This study highlights a substantial risk of CAR-T failure, with targeted therapies and immunotherapies commonly used post-CAR-T. OOP costs were significant, particularly for patients requiring additional therapy, with considerable variability. These findings emphasize the need for strategies to improve outcomes and reduce financial toxicity in this population."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma

Immune-targeted Combination With Chemotherapy for Acute Leukemia of Ambiguous Lineage (clinicaltrials.gov) - P=N/A | N=50 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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

Molecular characterization and predictors of relapse in patients with Ph + ALL after frontline ponatinib and blinatumomab. (PubMed, J Hematol Oncol) - P2 | "WBC ≥ 70 × 109/L is a high-risk feature in patients with Ph + ALL receiving frontline blinatumomab and ponatinib and may supersede the prognostic importance of baseline molecular features. Alternative frontline treatment strategies may be needed for these patients to reduce the risk of relapse and improve long-term outcomes."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CD19 • IKZF1 • VPREB1

Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Mar 2025 ➔ Feb 2027

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Barriers to Blinatumomab Administration and Access: How to Overcome Them (ASCO 2025) - No abstract available

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

FIRST-IN-HUMAN STUDY OF ASCIMINIB (ASC) MONOTHERAPY IN ADULTS WITH RELAPSED/REFRACTORY (R/R) PHILADELPHIA-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (PH+ ALL) (EHA 2025) - P1, P2 | "Pts were heavily pretreated: 89.3% (n=25) had ≥2 prior TKIs, 53.6% (n=15) had prior ponatinib treatment, and 46.4% (n=13) had relapse post transplant. In the current analysis, ASC monotherapy in heavily pretreated pts with Ph+ ALL demonstrated antileukemic activity and was well tolerated, with favorable safety, consistent with parallel studies of ASC in pts with CML. Additional phase 1 cohorts showed that dual treatment with ASC and dasatinib is safe for pts with Ph+ ALL. Ongoing trials are exploring the combination of ASC and blinatumomab (NCT06308588) and ASC with dasatinib, blinatumomab, and steroids (NCT03595917)."

Clinical • Monotherapy • P1 data • Acute Lymphocytic Leukemia • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

Design of the First Clinical Trial of AAV Gene Therapy in Immuno-Oncology (SENTRY-ALL): A Single Dose CD3/CD19 Bi-Specific T-Cell Engager for the Treatment of CD19+ B-Cell Acute Lymphoblastic Leukemia (ASGCT 2025) - P1/2 | "VNX-101 is an investigational adeno-associated virus (AAV) gene therapy developed to express a secreted anti-CD19/anti-CD3 scFv diabody (termed GP101)...Prior blinatumomab and/or CD19 CAR T-cell treatment is allowed...This trial aims to provide the first clinical experience in the use of AAV gene therapy as a new paradigm for cancer immunotherapy. Disease Focus of Abstract:Cancer Hematologic"

Clinical • Gene therapy • Immuno-oncology • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Meta-analysis of the cardiovascular adverse effects of bispecific antibodies in malignant hematology therapies. (ASCO 2025) - "The BsAbs in this analysis were blinatumomab, elranatamab, epcoritamab, glofitamab, mosunetuzumab, talquetamab, and teclistamab and only monotherapy regimens were included. As BsAbs have demonstrated promising efficacy and increased use in the treatment of R/R hematologic malignancies, a wide variety of cardiac toxicities have been observed in these patients and more data on these toxicities are documented. This meta-analysis has identified tachycardia, cardiac arrhythmias, and hypotension as the most significant cardiac adverse events in a pooled analysis of multiple BsAbs. Practicing oncologists, cardiologists, and pharmacists need not only to be aware of these potential toxicities, but also to establish strategies for cardiac monitoring, prevention and management in order to provide quality care to cancer patients."

Adverse events • Retrospective data • Acute Lymphocytic Leukemia • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Hypertension • Hypotension • Leukemia • Lymphoma • Multiple Myeloma • Myocardial Infarction • Non-Hodgkin’s Lymphoma • Oncology

Role of External Control Arm (ECA) Derived from Real World Data (RWD) in US FDA Regulatory Approval from 2020-2024 (ISPOR 2025) - "OBJECTIVES: To analyze role of ECA in US FDA approvals ( 2020 - 2024) & summarize the key disease areas leveraging ECA. systematic literature review and analysis of all novel drug approvals including NDA (New Drug Application) and BLA (Biological License Application)submitted from 2020-2024 were analyzed. The percentage of approvals involving external control arms increased steadily, particularly in rare diseases, oncology, and conditions with small or hard-to-recruit patient populations from 2020-2024 2020: Early Exploration (5-7% of Approvals) : 1.Ibrance (palbociclib): Used retrospective RWD to support male breast cancer indication...Blincyto (blinatumomab): Supplemental approvals for rare cancers based on external data. 2021: Accelerated Adoption Amid COVID-19 (10-15% of Approvals) 1.Veklury (remdesivir): Approval supported by real-world hospital data as external comparisons...Keytruda (pembrolizumab): Label expansion for certain cancers using external control..."

Clinical • Real-world • Real-world evidence • Alzheimer's Disease • Breast Cancer • CNS Disorders • Genetic Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Male Breast Cancer • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Oncology • Rare Diseases • Solid Tumor • HER-2

Outcomes of Ph-like B-lineage acute lymphoblastic leukemia in the era of novel therapies. (ASCO 2025) - "The remaining 20% of pts received novel therapies in first-line setting, including C10403 + inotuzumab (InO) in 7%, ino + blinatumomab (blin) in 6%, hyperCVD + venetoclax in 4% and C10403 + imatinib in 3%...Of note, 5 pts received kinase inhibitors (ruxolutinib, dasatinib, imatinib) in salvage setting, but did not achieve remission... Ph-like B-ALL pts treated with standard chemo have lower CR and RFS rates. Adding novel agents (InO, blin, venetoclax) to upfront regimens may improve outcomes. Future studies should focus on optimal first-line combinations and higher-risk groups such as KRAS-mutated Ph-like B-ALL."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ABL2 • CDKN2A • CRLF2 • CSF1R • FGFR • IKZF1 • JAK2 • KRAS • NRAS • PAX5 • ROS1

HEALTH-RELATED QUALITY OF LIFE BENEFITS OF FRONTLINE PONATINIB PLUS BLINATUMOMAB IN ADULT PATIENTS WITH PH+ ACUTE LYMPHOBLASTIC LEUKEMIA. PRELIMINARY ANALYSIS OF THE GIMEMA ALL2820 TRIAL (EHA 2025) - "We report the first evidence-based data on HRQoL of adult patients with newly diagnosed Ph+ ALL treated in induction/consolidation with ponatinib plus blinatumomab. Our findings indicate notable HRQoL improvements across all age groups, although younger patients seem to benefit the most from this novel treatment approach, devoid of systemic chemotherapy. Further analyses will elucidate on the value of this approach compared with standard of care."

Clinical • HEOR • Acute Lymphocytic Leukemia • Fatigue • Hematological Malignancies • Leukemia • Oncology • Pain • Pulmonary Disease

Fibroblast Activation Protein (FAP) Directed Bispecific Antibodies Target Pediatric Sarcomas (ASGCT 2025) - "We developed a bispecific antibody construct that combined the anti-FAP scFv from clone BIBH 1 (sibrotuzumab) with that of the anti-CD3 scFV LK2-07 (blinatumomab)...Coupled with our lab's novel rAAV expression system, this approach shows promise as a targeted therapy against CAFs and FAP-expressing sarcomas, though further in vivo studies are needed to assess its anti-tumor efficacy. Disease Focus of Abstract:Cancer Solid Tumors"

Clinical • IO biomarker • Fibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor • CAFs • FAP

Development of an Adeno-Associated Virus Expressing a Secreted T Cell Engager for Long-Term B Cell Ablation with High Transgene Expression to Minimize Vector Dose (ASGCT 2025) - "Serum levels of GP101 were consistently above the lower threshold of the human therapeutic target range (300 pg/mL, based on clinical experience with blinatumomab) at doses of 3.0E10 vg/kg (females) and 1.0E10 vg/kg (males). Based on the mechanism of action, VNX-101 may also be applicable to B cell lymphoma, chronic lymphocytic leukemia, and autoimmune diseases. Disease Focus of Abstract:Cancer Hematologic"

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Gene Therapies • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CD22/CD19 CAR-T and Blinatumomab Combined With Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Soochow University

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology

Treatment of Older Patients With ALL. (PubMed, Am Soc Clin Oncol Educ Book) - "In Ph-negative ALL, the duration and intensity of chemotherapy was reduced, and outcomes improved with the addition of inotuzumab ozogamicin (InO) and blinatumomab into the frontline setting...The combination of blinatumomab and ponatinib induced high rates of complete molecular responses and excellent survival, without reliance on HSCT. A subset of patients with elevated WBC count at diagnosis are at particular risk of CNS and systemic relapse and may require additional strategies such as incorporating one to two cycles of high-dose methotrexate/cytarabine into consolidation, and potentially CAR T cells. In T-cell ALL, adding venetoclax into the frontline setting has improved outcomes. In early T-cell precursor ALL, HSCT is still needed. To further improve outcomes in older patients, novel agents such as subcutaneous blinatumomab, CAR T cells, newer-generation TKIs, and menin inhibitors should be investigated in the frontline setting."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation • ABL1