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

Blinatumomab in combination with olverembatinib and concurrent intrathecal chemotherapy successfully treated a chronic myeloid leukemia relapse with central nervous system blast crisis: case report and literature review. (PubMed, Ann Hematol) - "The combination of blinatumomab, olverembatinib, and concurrent intrathecal chemotherapy may be an effective treatment strategy for CML progression, particularly in cases with CNS involvement."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Retrospective Study Shows Variability of Interventions for Blinatumomab-Related Neurotoxicity in Hematologic Malignancies (OncLive) - "Among patients with hematologic malignancies receiving blinatumomab (Blincyto), a higher incidence of symptoms consistent with immune effector cell–associated neurotoxicity syndrome (ICANS) was reported compared with that of prior research, indicating the need for a more objective tool for assessing and grading neurotoxicity, according to data from a retrospective cohort study presented at the 50th Annual Oncology Nursing Society Congress. Of 28 patients who received blinatumomab, 57% experienced any neurotoxicity, and 46% had any aphasia and/or encephalopathy. Approximately 25% of aphasia and/or encephalopathy events were grade 3. Data showed that the most common neurotoxicity symptoms included headache (69%), encephalopathy (69%), tremors (63%), and aphasia (38%)."

Adverse events • Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies

KMT2A-rearranged acute lymphoblastic leukemia in infants: current progress and challenges. (PubMed, Haematologica) - "However, recent advances adding immunotherapy in the form of the bi-specific T-cell engager blinatumomab to the treatment led to encouraging results. In the present review we describe the current progress made, as well as the challenges that still lie ahead in terms of drug-related toxicity, the implementation of less toxic agents, acquired drug resistance, central nervous system involvement, and lineage switches. In addition, we touch upon the benefit of preclinical models that can assist in guiding new treatment strategies."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A

A Study of onCARlytics (CF33-CD19) in Combination With Blinatumomab in Adults With Advanced or Metastatic Solid Tumors (OASIS) (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Imugene Limited | N=33 ➔ 50

Enrollment change • Oncology • Solid Tumor

Assessment of Conditional Listing for Highly Uncertain and High-Priced Drugs in Taiwan (ISPOR 2025) - "The review and assessment process were conducted independently by two researchers. A total of 12 drugs were considered for conditional listing between 2022 and 2024, which included Pemazyre, Tepmetko, Qarziba, Kymriah, Vitrakvi, Blincyto, Vydamax, Takhzyro, Polivy, Velexbru, Spevigo, and Koselugo. The conditional listing opens up new opportunities for high-priced drugs. However, the 2-year real-world evidence for Pemazyre remains insufficient for the government to make a final reimbursement decision. Consequently, the results of the HTA will pose challenges in the future in Taiwan."

IndEx-2: An in vitro model to evaluate the impact of target antigen density on antibody and immune therapeutics (AACR 2025) - "In the first, we have compared CLN978, a novel CD19- TCE developed for B-cell malignancies and autoimmune diseases, with Blinatumomab and demonstrated that the former retained its activity in terms of cytotoxicity and cytokine production at much lower levels of CD19 expression and estimate the threshold for each molecule in a cohort of 10 healthy donors. The tandem CAR exhibited enhanced cytotoxicity when either or both antigens were expressed, whereas the dual CAR required co-expression of both antigens for optimal T-cell activation. These results underscore IndEx-2's robustcapability to evaluate the influence of antigen density on therapeutic safety andefficacy, providing a powerful tool for the development of antibody-based and immune-targeting cancer therapies."

IO biomarker • Preclinical • Hematological Malignancies • Oncology • CD19 • CD22 • HER-2 • IFNG

Beyond antibodies and CAR-T: CC312, a first-in-class, anti-CD19, anti-CD3, anti-CD28 trispecific antibody in treatment with relapsed and/or refractory B-cell malignancies (AACR 2025) - "In this study, CC312 exhibited key advantages over leading CD3xCD19 TCE blinatumomab in multiple clinically relevant in vitro functional assays, demonstrated robust tumor growth inhibition in B cell lymphoma mouse models and achieved thorough depletion of CD19+ B cells and potent activation of T cells in B cell lymphoma patients across dosages while maintaining a favorable safety/tolerability profile. Therefore, via its "Two Signal" co-stimulation approach, CC312 represents a promising candidate for treatment of B cell lymphoma. CC312's clinical benefit will continue to be explored at higher doses as part of ongoing Ph1a dose escalation study."

Trispecific • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD34 • CD8

Efficacy and safety comparison of CAR-T and blinatumomab immunotherapy as bridge-to-transplant strategy in relapsed/refractory B cell acute lymphoblastic leukemia (AACR 2025) - "CAR-T and Blinatumomab therapies demonstrate comparable safety and efficacy as bridging treatments to HSCT in patients with R/R B-ALL. Further studies are needed to optimize these treatment strategies."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD22

Characteristics of second primary malignancies following bispecific antibodies therapy. (PubMed, J Immunother Cancer) - "Our study provides the first detailed characterization of SPMs post-BsAb, underscoring the need for continued pharmacovigilance and individualized risk management to mitigate SPM risks in patients undergoing BsAb therapy."

Journal • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Chinese Children’s Cancer Group-2025 Protocol for Newly Diagnosed Low Risk Childhood B-cell Acute Lymphoblastic Leukemia (ChiCTR) - P2/3 | N=2325 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.; Institute of Hematolog

New P2/3 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

AN UNCOMMON CASE OF SECOND ALLOGENEIC HSCT FOR DONOR CELL LEUKEMIA: FEASIBILITY AND OUTCOME (EBMT 2025) - "She achieved CR with undetectable minimal residual disease (MRD) after Acute Lymphoblastic Leukemia (ALL)-like chemotherapy followed by bispecific monoclonal antibody blinatumomab... The combination of Treosulfan (10g/m2 intravenous IV from day -4 to day -2) and Fludarabine (30mg/m2 IV from day -6 to day -2) was preferred as conditioning regimen over reduced intensity busulfan due to demonstrated superior outcomes and reduced organ toxicity. Graft versus host disease (GVHD) prophylaxis included post-transplant cyclophosphamide, mofetil mycophenolate and cyclosporine...On day +129 our patient was hospitalized because of steroid refractory intestinal GVHD successfully treated with ruxolitinib... This case seems to confirm the importance of dysfunctional BM niche which plays a key role in developing hematologic malignancies. DCL cases offer the opportunity to study in vivo pathways underlying interaction between leukemia cells and BM immune-microenvironment.Furthermore, the..."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • DNMT3A • RUNX1

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

DONOR-DERIVED CAR-T CELLS IN CHILDREN WITH B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA RELAPSING AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: REPORT OF 22 CASES (EBMT 2025) - "Twenty had BCP ALL, 2 had B cell lymphoblastic Lymphoma with BM involvement, all relapsing after multiple lines of treatment, including previous HSCT(n=22), blinatumomab (n=18), inotozumab (n=4) and CAR-T cell infusion(n=6)...Lymphodepletion included fludarabine, cyclophosphamide +/- cytarabine, 8 pts received prophylactic tocilizumab at day-1, 14 pts received abatacept at days -1, +7, +14, +28The first CAR-T cell doses were 100х103/kg (n=20), 160х103/kg (n=1), 350х103/kg (n=1), 7 patients received 2nd dose 100x103/kg (n=2), 500x103/kg (n=1) and 900x103/kg(n=4) within median 10 days after first infusion... Our experience suggests that donor-derived lymphoid antigen-directed CAR-T cells expand in vivo and provide CR with manageable safety profile. Optimal consolidation should be further developed."

CAR T-Cell Therapy • Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Transplantation • CD22

EXACERBATION OF MITRAL VALVE REGURGITATION IN A B-ALL PATIENT UNDERGOING IMMUNOTHERAPY - Ushma Majmudar (ACC 2025) - "Background: T cell therapy (TCT) rarely causes isolated severe valvular pathology without cardiomyopathy, but its hemodynamic effects can considerably exacerbate mitral regurgitation (MR) in patients with subtle valvular issues.Case: A 48-year-old woman with a history of fenfluramine (FF) use for weight loss 10 years prior developed a cryptogenic stroke and 5 months later, was diagnosed with B-ALL...After her second blinatumomab (BL) cycle, she developed dyspnea... We emphasize the importance of considering prior FF use when evaluating patients with idiopathic MR. We also demonstrate how hemodynamic changes from TCT can worsen MR and show how careful hemodynamic management can enable the safe resumption of these lifesaving therapies."

Clinical • Cardiomyopathy • Cardiovascular • Metabolic Disorders • Pulmonary Disease • IL6

Efficacy and safety comparison of CAR-T and blinatumomab immunotherapy as bridge-to-transplant strategies in relapsed/refractory B cell acute lymphoblastic leukemia. (PubMed, J Transl Med) - "CAR-T and blinatumomab therapies demonstrate comparable safety and efficacy as bridging treatments to HSCT in patients with R/R B-ALL. Further studies are needed to optimize these treatment strategies."

Clinical • Journal • Retrospective data • 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 • Infectious Disease • Leukemia • Oncology • Transplantation • CD22

OUTCOMES OF CAR T-CELL THERAPY (CART19) FOR B-ALL: A GOCART COALITION REPORT ON BEHALF OF THE PDWP, ALWP, AND CTIWP OF THE EBMT (EBMT 2025) - " A total of 345 B-ALL patients (173 adults and 172 paediatrics) received therapy with Kymriah (65%), ARI-0001 (26%), Tecartus (5.5%), and others (3.5%), with a reverse Kaplan-Meier median follow-up of 2.2 years...Notably, this association was lost in alloHCT-exposed patients, with no impact for prior blinatumomab exposure and response. Prior inotuzumab refractoriness was strongly associated with worse 2-year OS and LFS for both alloHCT-naïve and alloHCT-exposed patients (p≤0.003), although inotuzumab-responsive and inotuzumab-naïve patients showed comparable outcomes... Commercial and academic CART19 therapy remains an effective treatment for adult and paediatric B-ALL patients. This "real-world" study suggests that efficacy is more impacted by prior refractoriness and disease burden than by age, preceding therapy, or cytogenetics. Also, the relevance of preceding factors and the biology affecting CART19 therapy might be different for..."

CAR T-Cell Therapy • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics

OUTCOMES OF PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA (R/R B-ALL) TREATED WITH OBECABTAGENE AUTOLEUCEL (OBE-CEL) WITH OR WITHOUT CONSOLIDATIVE ALLOGENEIC STEM CELL TRANSPLANTATION (SCT) (EBMT 2025) - P1/2 | "Patients received bridging therapy as appropriate and underwent lymphodepletion (fludarabine, 4×30mg/m2; cyclophosphamide, 2×500mg/m2), followed by tumour burden (TB)-guided split dosing (Days 1 and 10) to a total target dose of 410×106 CAR T-cells...Median number of prior therapies in both groups was two, with a higher rate of blinatumomab exposure (67% vs 32%), and lower rate of prior SCT (33% vs 51%) in transplanted vs non-transplanted patients... Despite small samples, this analysis demonstrates SCT does not appear to improve EFS/OS. Further studies could clarify optimal post-CAR T-cell management. Lower TB at lymphodepletion was associated with improved EFS without SCT."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

OBECABTAGENE AUTOLEUCEL (OBE-CEL) VERSUS EXTERNAL CONTROL ARM (ECA) MATCHED COMPARISONS IN ADULT PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA (R/R B-ALL) (EBMT 2025) - P1/2 | "Efficacy and safety were compared for patients treated with obe-cel (modified intent-to-treat [mITT]) and all enrolled patients (intent-to-treat [ITT]) versus matched ECA patients treated with SOC (≥1 dose of blinatumomab, inotuzumab ozogamicin or salvage chemotherapies)... Obe-cel demonstrated higher ORR, longer OS and EFS versus SOC in matched ECAs, alongside a manageable safety profile. These data support a positive benefit-risk profile with obe-cel for the treatment of adult R/R B-ALL. Clinical Trial Registry: NCT04404660; https://www.clinicaltrials.gov/study/NCT04404660"

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

NAÏVE T CELL DEPLETED HAPLOIDENTICAL DONOR HCT WITH SELECTED USE OF BLINATUMOMAB FOR PEDIATRIC PATIENTS WITH HEMATOLOGIC MALIGNANCIES RELAPSED AFTER PRIOR TRANSPLANTATION (EBMT 2025) - P2 | " This phase II study (REF2HCT) evaluated the use of selectively depleted haploidentical grafts after reduced intensity conditioning consisting of ATG, cyclophosphamide, fludarabine, thiotepa, melphalan, and rituximab...Herein we report the outcomes of participants enrolled for relapse after prior HCT (Cohort 1) who received short-course (6 week) sirolimus as graft-versus-host disease (GVHD) prophylaxis... We aimed for robust early immune reconstitution and enhanced graft-versus-leukemia effect, while limiting severe GVHD by sequentially infusing haploidentical TCRαβ and CD45RA+ depleted grafts. While relapse and treatment-related morbidity remain concerns in this high-risk patient population, our preliminary analysis indicates that this strategy results in promising outcomes for pediatric patients undergoing subsequent transplant for post-HCT relapse. Clinical Trial Registry: NCT02790515"

Clinical • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics • Transplantation

INOTUZUMAB OZOGAMICIN IN CHILDREN WITH B-ALL, ​SINGLE CENTER EXPERIENCE (EBMT 2025) - "Defibrotide was started prophylactically in all patients using InO and undergoing transplantation; and hepatic veno-occlusive disease not detected in any of patients. The results of InO treatment show encouraging efficacy and safety. We suggest that InO shall be applied in children with CD22-positive B- ALL who are resistant to chemotherapy or blinatumomab."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Hepatology • Leukemia • Oncology • CD22

DONOR LYMPHOCYTE INFUSIONS FOR ACUTE LYMPHOBLASTIC LEUKEMIA: A RETROSPECTIVE SINGLE-CENTER ANALYSIS (EBMT 2025) - "They received a median of 4 DLIs (1-12); DLIs were given in association with TKI in Ph+ ALL, with blinatumomab in 1 Ph-ALL , with nelarabine in one T-ALL and off-label bortezomib in another...They received a median of 3 DLIs (2-4), with TKI in Ph+ B-ALL, inotuzumab in Ph- ALL and radiotherapy in T-ALL... Nearly 40% of ALL patients needed DLI, primarily for MRD positivity. DLI can be curative and safe, particularly in the prophylactic/pre-emptive setting and in combination with other therapies. Prospective trials are needed to assess their role in the era of MRD monitoring and novel agents."

Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

DONOR LYMPHOCYTE INFUSIONS FOR ACUTE LYMPHOBLASTIC LEUKEMIA: A RETROSPECTIVE SINGLE-CENTER ANALYSIS (EBMT 2025) - "They received a median of 4 DLIs (1-12); DLIs were given in association with TKI in Ph+ ALL, with blinatumomab in 1 Ph-ALL , with nelarabine in one T-ALL and off-label bortezomib in another...They received a median of 3 DLIs (2-4), with TKI in Ph+ B-ALL, inotuzumab in Ph- ALL and radiotherapy in T-ALL... Nearly 40% of ALL patients needed DLI, primarily for MRD positivity. DLI can be curative and safe, particularly in the prophylactic/pre-emptive setting and in combination with other therapies. Prospective trials are needed to assess their role in the era of MRD monitoring and novel agents."

Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

A PHASE I/II STUDY OF TAFASITAMAB FOR THE PREVENTION OF RELAPSE AFTER STEM CELL TRANSPLANTATION IN PEDIATRIC PATIENTS WITH ALL (EBMT 2025) - P1/2 | "The majority of patients had received prior immunotherapies, including blinatumomab (n=7), inotuzumab ozogamicin (n=3) and CAR-T cell therapies (n=5). Based on the available data, long-term outpatient use of tafasitamab at a dose of 12 mg/kg body weight appears to be safe and well tolerated in pediatric patients with ALL at highest risk of relapse. Whether treatment with tafasitamab reduces the risk of relapse as anticipated can only be assessed in the further course of the study. Clinical Trial Registry: Clinicaltrials.gov: NCT05366218"

Clinical • P1/2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pediatrics • Transplantation

A PHASE I/II STUDY OF TAFASITAMAB FOR THE PREVENTION OF RELAPSE AFTER STEM CELL TRANSPLANTATION IN PEDIATRIC PATIENTS WITH ALL (EBMT 2025) - P1/2 | "The majority of patients had received prior immunotherapies, including blinatumomab (n=7), inotuzumab ozogamicin (n=3) and CAR-T cell therapies (n=5). Based on the available data, long-term outpatient use of tafasitamab at a dose of 12 mg/kg body weight appears to be safe and well tolerated in pediatric patients with ALL at highest risk of relapse. Whether treatment with tafasitamab reduces the risk of relapse as anticipated can only be assessed in the further course of the study. Clinical Trial Registry: Clinicaltrials.gov: NCT05366218"

Clinical • P1/2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pediatrics • Transplantation

B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS WITH RELAPSED/REFRACTORY OR PERSISTENT MRD BENEFIT FROM BLINATUMOMAB BRIDGING PRIOR TO ALLO-HSCT (EBMT 2025) - "Blinatumomab bridging to allo-HSCT is well tolerated in B-ALL patients. Patients who achieved MRD negativity had similar transplant outcomes regardless whether blina was bridged before allo-HSCT. For R/R B-ALL patients or patients with persistent MRD positivity, blina bridging provided equivalent transplant outcomes compared to patients who were chemotherapy sensitive."

Clinical • 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 • CD19