Blincyto (blinatumomab) / Astellas, Amgen, BeiGene - LARVOL DELTA

NCI-2021-01791: Venetoclax, Dasatinib, Prednisone, Rituximab and Blinatumomab for the Treatment of Newly Diagnosed or Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: OHSU Knight Cancer Institute | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Therapeutic Strategies for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients: Optimizing the Use of Monoclonal Antibodies. (PubMed, Eur J Haematol) - "The treatment landscape for relapsed or refractory acute lymphoblastic leukemia (RR ALL) has evolved significantly with the introduction of monoclonal antibodies such as blinatumomab and inotuzumab ozogamicin. As monoclonal antibodies increasingly move into frontline therapy, their role in relapse settings must be redefined. Future research should focus on unraveling the molecular underpinnings of resistance and refining treatment paradigms to improve survival and quality of life for patients with RR ALL."

Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Hepatology • Leukemia • Oncology • Transplantation • TP53

GRAAL-2024: A 3-cohort Randomized Study Evaluating the Role of New Immunotherapeutic Agents and of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Frontline Therapy of Adults With Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2/3 | N=1200 | Not yet recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris

New P2/3 trial • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Transplantation

Efficacy and Safety of Low-dose Chemotherapy Plus Immuno-targeted Drugs in Newly Diagnosed Elderly/Unfit Ph- B-ALL (clinicaltrials.gov) - P2 | N=53 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Infectious risks with blinatumomab exposure in B-cell acute lymphoblastic leukemia (ESCMID Global 2025) - No abstract available

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

Blincyto: Patent protection related to pharmaceutical compositions and bifunctional polypeptides in US until April 6, 2030 (Amgen) - Annual Report 2024: Patent protection related to method of treatment in US until Aug 26, 2031; Patent protection related to method of treatment in EU until Nov 06, 2029; SPC in France, Germany, Italy, Spain and the UK until 2029

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

Tyrosine Kinase Inhibitor Post-Allogeneic Stem Cell Transplantation in Adult Philadelphia-Positive B-Acute Lymphoblastic Leukemia: State of the Art and Future Directions. (PubMed, Curr Issues Mol Biol) - "First-line therapy is increasingly adopting a chemo-free approach, combining tyrosine kinase inhibitors (TKIs) with immunotherapy-specifically blinatumomab-which has resulted in high rates of complete molecular responses and improved survival outcomes...However, there remains considerable uncertainty regarding which patients benefit most from this approach, the optimal TKI agents, dosing strategies, and the duration of maintenance therapy. In this review, we aim to consolidate the available evidence on this topic, analyzing it in the context of the most recent clinical experiences."

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

Treatment-free remission in nontransplanted patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. (PubMed, Cancer) - "The current findings suggest that TKI discontinuation may be safe for highly selected patients with Ph-positive ALL in first complete remission who maintain CMR for at least 48 months. Larger studies are needed to confirm these findings."

Journal • Retrospective data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1

Up-front Blinatumomab Improves MRD Clearance and Outcome in Adult Ph- B-lineage ALL: the GIMEMA LAL2317 Phase 2 Study. (PubMed, Blood) - P2 | "Blinatumomab should be considered as a standard component of induction/consolidation for adult Ph- B-ALL. ClinicalTrials.gov # NCT03367299."

Journal • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Impact of Minimal Residual Diseases Status and Depth of Response on Survival Outcomes in Blinatumomab-Treated Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis. (PubMed, Am J Clin Oncol) - "The findings show that blinatumomab is superior to standard chemotherapy in improving the OS and DFS of patients with R/R ALL. Furthermore, it has a more favorable safety profile, making it an effective alternative to conventional chemotherapy for managing R/R ALL."

Journal • Minimal residual disease • Retrospective data • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

B-Lymphoblastic Leukemia/Lymphoma Arising in Patients with Multiple Myeloma (USCAP 2025) - "6 patients received blinatumomab maintenance therapy, and 2 underwent allogeneic stem cell transplantation. B-ALL arises in a subset of MM patients treated with lenalidomide, and has some specific features such as BCR::ABL-negativity and high frequency of TP53 mutations. Further studies are warranted to elucidate the role lenalidomide may play in the pathogenesis of B-ALL as well as the potential clonal relationship between MM and B-ALL in these patients."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • IDH2 • KMT2A • KRAS • NRAS • TP53

Pediatric Pathology Cases where Molecular Analysis Saved The Day - Chisholm (USCAP 2025) - "He was treated with standard-of-care high risk therapy which included prednisone, vincristine, daunorubicin, pegylated asparaginase, cyclophosphamide, mercaptopurine, intrathecal cytarabine, and intrathecal methotrexate...Due to low level ClonoSEQ® positivity, he received blinatumomab after his third course of maintenance therapy...Flow cytometry of his CSF identified blasts (comprising ~7% of nucleated cells) with increased side scatter and expressing CD19, CD22, CD24, CD10, CD34 (mildly increased), CD38 (mildly dim), CD20 (dim), and CD45 (mildly dim). Morphological Findings: 5 Figure 1: Click to view full size Figure 1 Caption: Diagnostic bone marrow aspirate, 400X Figure 2: Click to view full size Figure 2 Caption: Diagnostic bone marrow aspirate, 400X b Figure 3: Click to view full size Figure 3 Caption: Diagnostic bone marrow clot section, 200X Figure 4: Click to view full size Figure 4 Caption: Diagnostic bone marrow clot section, 400X Figure 5: Click to view..."

Biomarker • Clinical • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pain • Pediatrics • ABL1 • ANPEP • CD19 • CD20 • CD22 • CD24 • CD33 • CD34 • CD38 • CD58 • CD9 • CDKN2A • ETV6 • KMT2A • MME • PBX1 • PTPRC • RUNX1 • TCF3

Blinatumomab in Treating Patients With B-cell Acute Lymphoblastic Leukemia With Minimal Residual Disease (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Sep 2025 ➔ Sep 2026

Minimal residual disease • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Safety data of blinatumomab + low-intensity chemotherapy for older adults with frontline acute lymphoblastic leukemia (JSMO 2025) - No abstract available

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Reduced-dose chemotherapy followed by blinatumomab for newly diagnosed philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia: a propensity-matched comparison with hyper-CVAD. (PubMed, Discov Oncol) - P2 | "Reduced-dose chemotherapy followed by blinatumomab improves remission rates, MRD negativity, and survival while reducing adverse events in newly diagnosed Ph-negative BCP-ALL patients compared to hyper-CVAD. This regimen offers a safer and more effective induction therapy option, warranting further investigation in larger trials."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Thrombocytopenia

Prolonged Hypogammaglobulinemia in a Child With Down Syndrome After Treatment of Acute Lymphoblastic Leukemia With Immunochemotherapy Including Blinatumomab. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal • Acute Lymphocytic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology

Comprehensive analysis of adverse events associated with T-cell engagers using the FAERS database. (PubMed, Expert Opin Drug Saf) - "Blinatumomab was the most reported TCE (n = 4,950), and Tarlatamab the least (n = 185)...Drug-specific signals included reproductive system and breast disorders (IC025: 2.74) and vascular disorders (IC025: 2.25) with Tebentafusp, renal and urinary disorders with Epcoritamab (IC025: 1.84), and eye disorders with Elranatamab (IC025: 1.81). Novel AEs were also uncovered, including secondary malignant neoplasms, vasogenic cerebral edema with Mosunetuzumab (IC025: 5.77, ROR025: 56.29), and hydronephrosis with Epcoritamab (IC025: 7.50, ROR025: 180.70). Early-onset events (0.5 - 9.5 days) were linked to four TCEs, while delayed-onset events (>20 days) were linked to five others. This study highlights diverse AE profiles of TCEs, providing insights for clinicians to optimize their safe use in practice."

Adverse events • Journal • Hematological Disorders • Hematological Malignancies • Nephrology • Oncology • Ophthalmology • Solid Tumor

Immune Cell Engagers: Advancing Precision Immunotherapy for Cancer Treatment. (PubMed, Antibodies (Basel)) - "Since the FDA approval of Blinatumomab in 2014, ICEs have transformed the oncology landscape, with nine FDA-approved products and numerous candidates in clinical trials. Despite challenges such as toxicity, resistance, and limited efficacy in solid tumors, ongoing research into advanced platforms and combination therapies highlights the growing potential of ICEs to provide personalized, scalable, and effective cancer treatments. This review investigates the mechanisms, platforms, research trends, and clinical progress of ICEs, emphasizing their pivotal role in advancing precision immunotherapy and their promise as a cornerstone of next-generation cancer therapies."

Journal • Review • Hematological Disorders • Oncology • Solid Tumor

Blinatumomab for Treatment of Refractory Myasthenia Gravis (clinicaltrials.gov) - P2/3 | N=2 | Not yet recruiting | Sponsor: Da, Yuwei, M.D.

New P2/3 trial • CNS Disorders • Myasthenia Gravis

Blincyto expands indication to Ph-negative BCP ALL consolidation therapy (Korea Biomedical Review) - "Amgen Korea said Tuesday that it has received approval from the Ministry of Food and Drug Safety (MFDS) for its acute lymphoblastic leukemia (ALL) drug Blincyto (blinatumomab) to expand its indication as consolidation therapy for Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (Ph-negative BCP ALL)....With this approval, Blincyto is available for up to four cycles as consolidation therapy in adult and pediatric patients with Ph-negative BCP ALL. Blincyto was previously approved for treating relapsed or refractory B-cell ALL and microscopic residual disease (MRD)-positive B-cell ALL. Blincyto's expanded indication is based on results from the E1910, AALL1731, AALL1331, and 20120215 studies."

Korea approval • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia

Comparison of Obecabtagene Autoleucel (obe-cel) Versus an External Control Arm (ECA) in Adult Patients (pts) with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) (TCT-ASTCT-CIBMTR 2025) - P1/2 | "Efficacy and safety outcomes were compared in pts treated with obe-cel (modified intent-to-treat [mITT]) and all enrolled pts (ITT) vs matched ECA pts treated with SOC (≥1 dose of blinatumomab, inotuzumab ozogamicin, or salvage chemotherapies)... Obe-cel demonstrated higher ORR and longer OS and EFS vs SOC in matched ECAs. Safety was comparable between treatment groups, demonstrating a positive benefit-risk profile of obe-cel for treatment of adult R/R B-ALL."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Inflammation • Leukemia • Oncology

Allogeneic Hematopoietic Cell Transplant Following Standard of Care Brexucabtagene Autoleucel (Brexu-cel) in Adults with B-Cell Acute Lymphoblastic Leukemia (B-ALL): Results from the Real-World Outcomes Collaborative of CAR T in Adult ALL (ROCCA) (TCT-ASTCT-CIBMTR 2025) - "Patients were heavily pre-treated with a median 3 lines of pre breux-cel therapy: 7 (16%) had prior alloHCT, 28 (64%) had prior blinatumomab, and 13 (30%) had prior inotuzumab. This study represents the largest report to date demonstrating feasibility and outcomes of consolidative alloHCT following commercial brexu-cel in adult B-ALL. Generally low rates of GVHD and NRM were noted in HCT-naïve patients, while NRM was high in a small cohort of patients who underwent second HCT. We did not identify any factors associated with EFS or OS in this cohort, although limited by sample size."

Clinical • IO biomarker • Real-world • Real-world evidence • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • ABL1

AMGEN REPORTS FOURTH QUARTER AND FULL YEAR 2024 FINANCIAL RESULTS (PRNewswire) - "BLINCYTO (blinatumomab) sales increased 58% year-over-year to $381 million in the fourth quarter and 41% for the full year, primarily driven by volume growth. Vectibix (panitumumab) sales decreased 2% year-over-year to $246 million in the fourth quarter, driven by 5% unfavorable foreign exchange impact and 4% lower volume, partially offset by higher net selling price. Sales increased 6% for the full year, driven by 8% higher net selling price and 4% volume growth, partially offset by unfavorable foreign exchange impact. KYPROLIS (carfilzomib) sales increased 6% year-over-year to $372 million in the fourth quarter and 7% for the full year, driven by volume growth outside the U.S."

Sales • Acute Lymphocytic Leukemia • Colorectal Cancer • Multiple Myeloma

Always more immunotherapy in the management of B-lineage acute lymphoblastic leukemia. (PubMed, Med) - "The high responses associated with the low incidence of grade ≥3 side effects make obe-cel an attractive candidate for a broader use of CAR-T cells in B-ALL. Its impact will have to be weighed with the monoclonal antibody blinatumomab in the frontline treatment of B-ALL."

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

Development of a policy model for pediatric acute lymphoblastic leukemia to facilitate economic evaluation. (PubMed, J Natl Cancer Inst) - "The ALL policy model can serve as a modeling foundation for timely economic evaluation. Introduction of blinatumomab in relapsed B-cell ALL may be a cost-effective strategy."

HEOR • Journal • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation