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

Ponatinib/blinatumomab for relapsed Philadelphia chromosome-positive leukemia as a bridge to allogeneic transplantation. (PubMed, Hematology) - "Case 1: A 60-year-old man with Ph + ALL achieved molecular complete remission (mCR) with Pona/BLIN after relapse following initial dasatinib-based treatment and subsequently underwent allo-HCT. Case 2: A 39-year-old man with Ph + ALL achieved hematological CR (hCR) with one cycle of inotuzumab ozogamicin and mCR with Pona/BLIN after post-transplant relapse but developed extramedullary relapse with BCR::ABL-negative clone and underwent a second allo-HCT in non-remission...None of the cases developed grade 3 or higher adverse events during treatment. These cases suggest that Pona/BLIN combination therapy is safe and effective as a bridging strategy to allo-HCT, but extramedullary relapse caused by BCR::ABL-negative blasts can occur."

Journal • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation

Bispecific Antibodies in Hematologic Malignancies: Attacking the Frontline. (PubMed, BioDrugs) - "Since blinatumomab's approval as the first bispecific antibody (BsAb) in cancer therapy, these immunomodulatory agents have achieved substantial success in lymphoid malignancies...In lymphoma, epcoritamab, glofitamab, and mosunetuzumab show proof-of-principle for complete remission (CR) without chemotherapy or cell-based treatment...In MM, teclistamab, talquetamab, and elranatamab achieve impressive CR rates in the relapsed setting and similarly, are being investigated in earlier line combinations and in precursor entities such as smoldering myeloma and monoclonal gammopathy of undetermined significance (MGUS). With a unique mechanism of action and continued testing in earlier lines, BsAbs are poised to be among the winners in the race to the frontline treatment of hematologic malignancies."

Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Monoclonal Gammopathy • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Smoldering Multiple Myeloma

TCRαβ-depleted Progenitor Cell Graft With Early Memory T-cell DLI, Plus Selected Use of Blinatumomab, in naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Oncology • Transplantation

Interfant-21 Treatment Protocol for Infants Under 1 Year With KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia (clinicaltrials.gov) - P3 | N=160 | Active, not recruiting | Sponsor: Princess Maxima Center for Pediatric Oncology | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A

CD19-ReTARGTPR: A Novel Fusion Protein for Physiological Engagement of Anti-CMV Cytotoxic T Cells Against CD19-Expressing Malignancies. (PubMed, Cancers (Basel)) - "Unlike CD19-directed CAR T cells or the CD19/CD3 BiTE blinatumomab, CD19-ReTARGTPR mediated robust cytotoxic activity without triggering supraphysiological cytokine release. Importantly, this approach retained efficacy even against cancer cells with low CD19 expression. In summary, we provide a robust proof-of-concept study and show that CD19-ReTARGTPR offers a promising alternative strategy for T cell redirection, enabling the selective and effective killing of CD19-expressing malignancies while minimizing cytokine-driven toxicities through physiological CTL activation pathways."

IO biomarker • Journal • Chronic Lymphocytic Leukemia • Cytomegalovirus Infection • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • B2M • CD19 • HLA-B

The proposal to expand reimbursement for Amgen Korea's Blincyto (blinatumomab) and the neutropenia treatment component pegfilgrastim, such as Neulasta by Kyowa Kirin Korea, has been approved by the CDRC. (Korea Biomedical Review) - "Blincyto establishes its reimbursement criteria for indications in the consolidation therapy of adult and pediatric patients with Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (ALL). At the same time, pegfilgrastim-containing formulations received coverage for treating febrile neutropenia and reducing the duration of neutropenia in patients undergoing cytotoxic chemotherapy for malignant tumors."

Reimbursement • B Acute Lymphoblastic Leukemia • Chemotherapy-Induced Neutropenia

CAR T cell therapy in acute lymphoblastic leukemia (PubMed, Inn Med (Heidelb)) - "Modern immunotherapy in the form of T‑cell-based CD19-targeted approaches, such as the approved bispecific T‑cell engager (BiTE antibody) blinatumomab and chimeric antigen receptor T cells (CAR T cells) with the approved products tisagenlecleucel and brexucabtagene autoleucel has revolutionized the treatment of B‑precursor acute lymphoblastic leukemia (ALL). Furthermore, resistance mechanisms are discussed and an outlook on further development is given. The T‑precursor ALL remains a challenge due to its immunological complexity but new developments in CAR-T cell treatment approaches targeting CD5 and CD7 show that progress is also being made in this area."

Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD5 • CD7

AALL1821: A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov) - P2 | N=461 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting | N=300 ➔ 461

Enrollment change • Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • CD19

A BISPECIFIC ANTI-FLUORESCEIN X ANTI-CD3 T-CELL ENGAGER ANTIBODY IN COMBINATION WITH FLUORESCEINATED ADAPTORS ENABLES LYSIS OF NEOPLASTIC CELLS (EHA 2025) - "We engineered a bispecific T-cell engager (AdFITC-TCE) by combining sequences from the fully human anti-fluorescein antibody E2 and the anti-human CD3 antibody OKT3 into a tandem single-chain variable fragment format, analogous to the design of blinatumomab. We generated antibody adaptors by conjugating fluorescein to diabodies against CD33 and CD117 and to the clinical-grade IgGs rituximab (anti-CD20) and daratumumab (anti-CD38)... Collectively, these data demonstrate that AdFITC-TCE, in combination with fluoresceinated antibody binders, activates T-cells, leading to respective target cell lysis. In theory, this approach would allow the use of any cell surface binder that can be fluoresceinated as an adaptor for T-cell mediated lysis of target cells."

Combination therapy • Acute Myelogenous Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD33 • CD3E • KIT

GMALL-BLIVEN: Venetoclax in Addition to Blinatumomab in Adult Patients With Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) (clinicaltrials.gov) - P1/2 | N=30 | Active, not recruiting | Sponsor: Goethe University | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Apr 2026 | Trial primary completion date: Jun 2025 ➔ Apr 2026

Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Study to Investigate Intravenous Blinatumomab in Japanese Adult Participants With Newly Diagnosed Philadelphia-negative B-precursor Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting | N=10 ➔ 6

Enrollment change • Enrollment closed • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Fragment-Based Immune Cell Engager Antibodies in Treatment of Cancer, Infectious and Autoimmune Diseases: Lessons and Insights from Clinical and Translational Studies. (PubMed, Antibodies (Basel)) - "Since the advent of recombinant DNA technologies and leading up to the clinical approval of T cell engager blinatumomab, the modular design of therapeutic antibodies has enabled the fusion of antibody fragments with proteins of various functionalities...While many reviews have provided outstanding summaries of preclinical phase fbAbs and cataloged relevant clinical trials, to date, very few of the articles in searchable databases have comprehensively reviewed the details of clinical outcomes along with the underlying reasons or potential explanations for the success and failures of these fbAb drug products. To fill the gap, in this review, we seek to provide the readers with clinically driven insights, accompanied by translational and mechanistic studies, on the current landscape of fragment-based immune cell engager antibodies in treating cancer, infectious, and autoimmune diseases."

Journal • Review • Immunology • Oncology

Analysis of 8 children with TCF3:: HLF fusion gene positive acute lymphoblastic leukemia (PubMed, Zhonghua Er Ke Za Zhi) - "Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy."

IO biomarker • Journal • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Endocrine Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Musculoskeletal Pain • Oncology • Pain • Transplantation • TCF3

Neurofibromatosis Type 1 with Relapsed/Refractory Precursor B-Lymphoblastic Lymphoma: Case Report and Literature Review. (PubMed, Case Rep Oncol) - "The child underwent umbilical cord blood transplantation after completing two sessions of blinatumomab therapy and is still disease-free to date. The findings from this study will offer valuable empirical references for peers treating NF1 associated with refractory/relapsed B-LBL."

Journal • Genetic Disorders • Hematological Malignancies • Immunology • Lymphoma • Musculoskeletal Pain • Neurofibromatosis • Oncology • Pain • Solid Tumor • Transplantation • NF1

Caregiving for Children With Acute Lymphoblastic Leukemia Receiving Home-Based Blinatumomab: Caregiver Experiences and Recommendations. (PubMed, Pediatr Blood Cancer) - "Caregivers can confidently manage home-based continuous infusion blinatumomab with anticipatory guidance and support, and with attention paid to context-related modifiers to care. Caregiver insights should be reflected in the principles that become the basis of future pediatric B-cell ALL clinical trials and care."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Mood Disorders • Oncology • Pediatrics • Psychiatry

Efficacy of Blinatumomab in Pediatric Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Cureus) - "These findings suggest that blinatumomab offers significant therapeutic advantages over conventional chemotherapy in pediatric patients with ALL, providing improved survival outcomes and reduced relapse rates. The results support the integration of blinatumomab into treatment protocols for children with ALL, particularly those at high risk of relapse or with refractory disease."

Journal • Retrospective data • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Can Be Treated With Chemotherapy-Free Regimens Without Transplant. (PubMed, Clin Lymphoma Myeloma Leuk) - "Outcomes were significantly improved with the combination of blinatumomab and ponatinib...Combinations of newer TKIs (such as asciminib or olverembatinib) with blinatumomab (intravenous, subcutaneous) might further improve outcomes and are being explored. Achieving durable NGS MRD negativity can identify patients at low risk of relapse who might be candidates for treatment discontinuation. In this review, we discuss the current progress in the management of Ph-positive ALL, particularly the role of chemotherapy-free regimens in mitigating the need for HSCT."

Journal • Review • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1 • IKZF1

Chemotherapy-free treatment of B-lymphoid/myeloid mixed phenotype acute leukemia: two case reports and literature review. (PubMed, Immunotherapy) - "This case report presents two cases of B-lymphoid/myeloid MPAL with MLL-AF4 genetic abnormality successfully treated with a chemo-free regimen composed of venetoclax, hypomethylating agents, and blinatumomab and achieved complete remission (CR). Considering the results of this case report, the combination of a chemotherapy-free regimen could be considered a safe and effective treatment approach for patients with B-lymphoid/myeloid MPAL."

Journal • Hematological Malignancies • Leukemia • Oncology • AFF1

Incorporation of Immunotherapy Into Adult B-Cell Acute Lymphoblastic Leukemia Therapy. (PubMed, J Natl Compr Canc Netw) - "Herein, we review the incorporation of blinatumomab and/or inotuzumab ozogamicin into frontline B-ALL regimens, including the potential use of chemotherapy-free approaches in select patient subgroups. We also explore the potential role of CAR T-cell therapies in the frontline setting for high-risk patients, as well as novel strategies to further improve outcomes in patients with B-ALL."

Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Effects of different B-cell-depleting strategies on the lymphatic tissue. (PubMed, Ann Rheum Dis) - "Protein-based B cell depletion reduces but usually does not deplete B cells in lymph nodes leaving the follicular architecture intact and being associated with disease recurrence."

Journal • Immunology • Infectious Disease • CD68

Post-transplant maintenance with blinatumomab for children, adolescents, and young adults with relapsed and refractory B-cell acute lymphoblastic leukemia: results of phase I in SCT-ALL-BLIN21. (PubMed, Haematologica) - "Not available."

Journal • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Blinatumomab for Treatment of R/R or MRD-positive CD19-Positive MPAL (clinicaltrials.gov) - P2 | N=2 | Completed | Sponsor: University of Maryland, Baltimore | Active, not recruiting ➔ Completed | Trial completion date: Aug 2027 ➔ May 2025

Minimal residual disease • Trial completion • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

CD19xCD3 T-cell engager blinatumomab effective in refractory generalized myasthenic syndromes. (PubMed, Mol Ther) - "Both patients experienced grade 1 cytokine release syndrome during initial treatment phases, but no neurotoxicity or severe adverse events were observed. This report underscores the potential of CD19xCD3 T-cell engagers as a promising therapeutic approach in severe autoimmune neuroimmunological disorders, warranting further investigation in clinical trials and mechanistic studies."

IO biomarker • Journal • CNS Disorders • Immunology • Inflammation • Myasthenia Gravis

Creating a Blinatumomab Care Guideline to Improve Ǫuality of Care in Patients Receiving Blinatumomab (APHON 2025) - No abstract available

Clinical

Efficacy of Blinatumomab in the Treatment of Pediatric B-cell Acute Lymphoblastic Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi) - "Blinatumomab can be used as a safe and effective treatment for inducing deep remission in pediatric R/R-ALL patients and as a bridge therapy for the pediatric ALL patients who are intolerant to chemotherapy."

Journal • Retrospective data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation