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

Impact of high-sensitivity next-generation sequencing, measurable residual disease and subsequent stem cell transplant in patients receiving blinatumomab for MRD-positive B-cell acute lymphoblastic leukemia. (PubMed, Haematologica) - "Not available."

Biomarker • Journal • Minimal residual disease • Next-generation sequencing • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Impact of measurable residual disease on outcomes using a modified DFCI protocol for adults with BCR-ABL negative acute lymphoblastic leukemia. (PubMed, Leuk Res) - "In conclusion, MRD is a significant predictor of outcomes with DFCI. DFS and OS are high in MRD negative patients, without the use of blinatumomab."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pediatrics • Septic Shock • Transplantation • ABL1 • BCR

Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL (clinicaltrials.gov) - P=N/A | N=100 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

IO biomarker • New trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCL2

Two birds, one BiTE: blinatumomab achieves concurrent B-ALL control and EBV clearance in post-HSCT patients: two cases report. (PubMed, BMC Pediatr) - No abstract available

Journal • Bone Marrow Transplantation • Epstein-Barr Virus Infections • Transplantation

Venetoclax plus inotuzumab ozogamicin for relapsed and refractory ALL: Results of a phase I trial (ASH 2025) - P1 | "Due to distinct mechanisms of action and non-overlapping toxicities, we hypothesized that adding VEN to INO would be safe and effective. This investigator-sponsored phase I study (NCT05016947) enrolled pts ≥18 years with CD22+ (≥20% ofblasts) R/R ALL (≥5% bone marrow [BM] blasts) or lymphoblastic lymphoma (LBL, BM <5% blasts).Philadelphia chromosome-negative (Ph-) pts had received ≥1 line of therapy; Ph+ pts were ponatinib(PON)-refractory or ineligible...Dexamethasone (10 mg/m2) was given during Lead-In and D1-4 of C1 Induction...BH3 profiling showed that ptsMRD- by C2 had lower pre-treatment mitochondrial apoptotic priming.Of the 21 CR patients, 1 pt (KMT2Ar) progressed during C2, and the remaining 20 pts (95.2%) wereconsolidated with blinatumomab (n=9, 42.9%), SCT (n=14, 66.7%, 6 after blinatumomab), DLI (n=1), XRT(n=1), or POMP (n=1)... VEN can be safely added to INO in pts with R/R CD22+ ALL/LBL including Ph+ ALL, with a very high anddurable rate of MRD- CR...."

P1 data • CNS Disorders • Febrile Neutropenia • Gastrointestinal Disorder • Hepatology • Lymphoblastic Lymphoma • Lymphoma • Neutropenia • Thrombocytopenia • KMT2A

Short-duration blinatumomab for residual disease eradication as a bridge to transplant in B-ALL: Pediatric and adult outcomes in a resource-limited context (ASH 2025) - P=N/A, P2 | "Conditioning for children was melphalan-based plus 2 Gy total body irradiation (TBI) in haploidentical grafts; for adults 12 Gy total marrow andlymphoid irradiation (TMLI) (NCT06209190). Graft-versus-host disease (GVHD) prophylaxis was post-transplant cyclophosphamide, tacrolimus and mycophenolate...OS at 24 months was 63%, median NR (95% CI 22.97-43.15), EFS at 24 months was 55%, with amedian of 42 months (95% CI 4.39-79.60%). N=2 died after HCT in remission due to pneumonia and athromboembolic event.ConclusionsA short-course of blinatumomab is effective, demonstrating that it can be an adaptable alternative in low-and middle-income countries as a bridge to HCT for R/R patients in CR with detectable MRD."

Clinical • Residual disease • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Pediatrics • Pneumonia • Respiratory Diseases • Transplantation

BAFFR-CAR T cells (PMB-CT01) show promising safety and anti-leukemia efficacy in relapsed/refractory B-cell ALL patients after CD19-targeted therapy failure, including CD19-negative disease (ASH 2025) - P1 | "Introduction: Immunotherapies targeting CD19, such as blinatumomab and CAR T cells, have shownremarkable efficacy in relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL)...DL-1 (de-escalation) and DL1 (starting dose) consist ininfusion with 20M and 50M CAR T cells, respectively, after lymphodepletion (LD) with cyclophosphamideonly... BAFFR-CAR T cell therapy demonstrated an excellent initial safety profile. Following LD withcyclophosphamide and fludarabine, the 50M dose demonstrated robust expansion and promisingactivity in heavily pretreated pts with r/r B-ALL who had failed prior CD19-targeted therapies and hadlimited treatment options. Treatment successfully transitioned pts to potentially curative transplant."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • IL6

Real-world safety profile of T-cell engagers: evidence from multi-database analysis with CAR-T comparisons. (PubMed, Front Immunol) - "The TCE class showed profound drug-specific heterogeneity, including severe oral/nail toxicities with talquetamab (oral toxicity ROR = 6066.40) and extramedullary relapse/infiltration with blinatumomab. TCEs are characterized by rapid early CRS/TLS AEs, elevated infection reporting, and target-specific toxicities, while CAR-T exhibits stronger CRS/ICANS signals. These findings support early monitoring and molecule-specific, syndrome-based risk management, advancing precision pharmacovigilance for T-cell redirecting therapies."

Clinical • Journal • Real-world evidence • Infectious Disease • Oncology

Advances in Chemotherapy in Pediatrics Acute Lymphocytic Leukemia (Pall): Actions, Associated Risks and Emerging Therapies. (PubMed, Curr Pharm Des) - "Consequently, new methods of therapy are under exploration with targeted therapies like tyrosine kinase inhibitors, monoclonal antibodies (e.g., blinatumomab), and CAR T-cell therapy that promise to treat cancer without major side effects to normal cells...Even so, these therapies need to be thoroughly examined for safety, success, and their effects in children before being approved. In conclusion, while chemotherapy still forms the core of PALL therapy, realizing its side effect problems, suggests that we should look for better solutions using new targeted approaches, supportive herbal medicines, and individualized care plans that may greatly alleviate pediatric leukemia and improve overall health parameters of children with leukemia."

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

Addition of Inotuzumab to a Pediatric Inspired Chemotherapy Regimen in Young Adult Patients with B-Cell Acute Lymphoblastic Leukemia: Findings from the Alliance A041501 Phase 3 Randomized Trial (ASH 2024) - P3 | "Eligible pts received the CALGB 10403 regimen modified to omit extended induction, include dexamethasone as opposed to prednisone as steroid backbone, cap the pegaspargase dose to 3750 units, and adding rituximab for pts with CD20 expression (> 20%). INO may still be efficacious if late toxicity can be mitigated. A pilot study is planned that will decrease INO dose, add 2 cycles of blinatumomab and strict infectious prophylaxis guidelines."

Clinical • P3 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pediatrics • Septic Shock • ABL1 • CD20 • CD22

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

Updated results from the Phase 1b/2 study of MK-1045, a novel CD19xCD3 T-cell engager, in adult participants with relapsed or refractory B-cell acute lymphoblastic leukemia (ASH 2025) - P1/2 | "Introduction: MK-1045 (CN201) is a humanized bispecific IgG4 CD19xCD3 T-cell engager that has shownencouraging safety, tolerability, and preliminary efficacy in participants with relapsed or refractory (R/R)B-cell acute lymphoblastic leukemia (B-ALL) (Wang et al...Among participants withprior exposure to blinatumomab or CAR T-cell therapy who had received a target dose ≥60 mg, 5 of 5participants achieved CR/CRi/CRh and 4 achieved MRD negativity... The safety profile of MK-1045 in adult participants with R/R B-ALL has been generallymanageable with dose modifications and standard medical care. MK-1045 has shown encouraging singleagent antitumor activity in adult participants with R/R B-ALL, achieving a CR/CRi/CRh rate of 92% at the2/20/90 mg dose level."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia

Blincyto: Expiry of patents in China related to method of use in 2029 (BeOne Medicines) - Annual Report 2025: Expiry of patents in China related to combination use in 2031

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

IMMUNOTHERAPY UNDER THE MICROSCOPE: CARDIO-RENAL OUTCOMES OF CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY (CART) VS BISPECIFICS IN A REAL-WORLD PROPENSITY-MATCHED COHORT STUDY (ACC 2026) - "Background: No current large studies directly compare cardiac outcomes of bispecific antibodies (Teclistamab, Elranatamab, Talquetamab, Blinatumomab, Epcoritamab, Mosunetuzumab) and CAR T-cell therapies. CART therapy was associated with lower all-cause mortality and fewer cardiac and renal adverse events compared to bispecific antibodies, supporting its potential cardio-oncology safety advantage. Further prospective studies are warranted to validate these findings."

Bispecific • CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • Cardiovascular

Dermatologic adverse events with bispecific T-cell engager therapies (AAD 2026) - " Among solid-tumor-directed BiTEs, tebentafusp dAEs include early, diffuse exanthems with pruritus, xerosis, edema, and bullous changes in high-grade events (dAE 83-91%; pruritus 69%; grade ≥3 rash 16-21%); delayed depigmentation/vitiligo-like changes are also reported. Tarlatamab presents with low-grade morbilliform eruptions (rash 6%, grade ≥3 2%; pruritus 11%). Among BiTEs for hematologic malignancies, talquetamab results in a distinctive mucocutaneous dAE profile involving hand-foot syndrome, nail changes (56%) including onychomadesis and onychodystrophy, dysgeusia (72%), and xerostomia (36%); dAE-related discontinuation is <1%. Mosunetuzumab leads to rash in 34-39% (grade ≥3 4%) and injection-site reactions in 53%. With blinatumomab, infusion-type exanthems predominate (7-16%; ≥ grade 3 ~1%); medium-vessel vasculitis and peri/subungual pyogenic granulomas have also occurred. For elranatamab, injection-site reactions (37%) and secondary cutaneous malignancies..."

Adverse events • Bispecific • IO biomarker • Dental Disorders • Hematological Malignancies • Immunology • Pruritus • Skin Cancer • Solid Tumor • Vasculitis • Vitiligo • Xerostomia

A phase I study of asciminib in combination with dasatinib, prednisone, and blinatumomab for Ph-positive acute leukemia in adults. (ASCO 2025) - P1 | "Dual ABL1 inhibition with ASC and DAS can be safely combined with blin in Ph+ acute leukemia. An additional 25-pt cohort is planned with blin in combination with DAS and ASC at optimized doses. Response kinetics."

Clinical • Combination therapy • P1 data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Respiratory Diseases • IKZF1

Inotuzumab ozogamicin then blinatumomab for older adults with newly diagnosed, ph-negative, CD22-positive, B-cell acute lymphoblastic leukemia: Extended follow-up of alliance for clinical trials in oncology A041703 cohort 1 reveals durable remission and survival (ASH 2025) - "Longer follow-up of chemotherapy-free treatment with InO and blina for older pts withnewly diagnosed, Ph-negative, CD22-positive, B-cell ALL reveals durable remissions and survival. TheA041703 regimen is a compelling option for first-line treatment of this pt population.Support: U10CA180821, U10CA18088; https://acknowledgments.alliancefound.org."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Breast Cancer • CNS Disorders • Hematological Malignancies • Hepatology • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Solid Tumor • CD22 • TP53 • ZNF384

CD19 CAR T cell therapy is an effective strategy for first CNS relapse in pediatric b ALL (ASH 2025) - P2 | "Introduction: The 4-year disease-free survival (DFS) of children with first isolated central nervous system(iCNS) relapse treated on the most recent Children's Oncology Group AALL1331 randomized phase 3 trialwas extremely poor at 24%, and the addition of blinatumomab failed to improve outcomes...We conducted a Phase 2 trial ofCTL019, the construct that was FDA approved as tisagenlecleucel, for this population (NCT04276870). Patients 0-29 years (y) of age with CNS relapse of B-ALL without receipt of cXRT for this relapsewere lymphodepleted with fludarabine/cyclophosphamide prior to infusion with 5x106 CART19 cells/kg...In this Phase 2 trial, CART19 achieved an 85% 2‑year EFS in CNS‑relapsed B‑ALL with 88% (38/43) ofpatients avoiding toxic cranial radiation, the SOC for CNS relapse for decades. While longer follow-up isneeded, the 4y EFS of 71% and OS of 93% in the 14 patients with 4+ years of follow-up is promising and issuperior to the outcomes on AALL1331...."

CAR T-Cell Therapy • Clinical • CNS Disorders • Epilepsy • Inflammation • Pediatrics

Efficacy and safety of short-course blinatumomab in patients with relapsed/refractory or MRD-positive B-cell acute lymphoblastic leukemia. (PubMed, Blood Cancer J) - No abstract available

Journal • Minimal residual disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Characterization and preclinical efficacy of a CD3×CD20 bispecific T cell engager in a humanized PBMC mouse model (AACR 2026) - "FDA-approved TCEs, such as Epcoritamab (CD3xCD20) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), Blinatumomab (CD3×CD19) for acute lymphoblastic leukemia (ALL) and Teclistamab (CD3×BCMA) for multiple myeloma, have demonstrated significant clinical efficacy in these respective diseases...Furthermore, both low and high doses of TCE resulted in a greater reduction in tumor volume compared to the ICI Toripalimab, a humanized PD-1 monoclonal antibody. Evidence of body weight loss (BWL) was observed in the groups that had PBMCs administered (tumour bearing animals), suggesting that the BWL is linked to the model and PBMC rather that the treatment. These findings highlight the potential of CD3×CD20 TCEs as an alternative strategy for treatment of Burkitt's lymphoma."

Bispecific • Preclinical • Acute Lymphocytic Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD20

Novel Treatment Combinations for B-ALL May Help Patients Safely Achieve Remission: With Colin Vale, MD (Apple Podcasts) - "In our exclusive interview, Dr Vale discussed data from a phase 2 trial (NCT03263572) evaluating blinatumomab (Blincyto) plus ponatinib (Iclusig) in patients with Philadelphia chromosome–positive B-cell acute lymphoblastic leukemia. In addition to underscoring the findings and their clinical significance, Vale expanded on how the combination can improve patient quality of life by helping patients avoid procedures like allogeneic stem cell transplant."

Audio

The growing armamentarium of agents for older adults with ALL (YouTube) - "Marlise Luskin, MD, MSCE...highlights the expanding treatment options for older adults with acute lymphoblastic leukemia (ALL), including inotuzumab ozogamicin and blinatumomab. She also comments on the potential of venetoclax as an alternative for patients who cannot receive inotuzumab or blinatumomab, and explains that combining available agents to create effective regimens is an ongoing investigative goal."

Interview • Video

Blinatumomab, inotuzumab & venetoclax in older patients with ALL: practical considerations (YouTube) - "Marlise Luskin, MD, MSCE...shares insights into the treatment of older adults with acute lymphoblastic leukemia (ALL), emphasizing the importance of improving efficacy while reducing toxicity in this patient population. Dr Luskin highlights the potential of agents such as inotuzumab ozogamicin, blinatumomab, and venetoclax, each with its own advantages and challenges, and notes that ongoing trials are investigating how to best combine these agents to achieve optimal outcomes."

Interview • Video

Blinatumomab consolidation in high-risk Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia in adults: Final report of the graall-2014/b-QUEST study. (ASH 2025) - "In conclusion, this study supports the use of blinatumomab consolidation in high-risk Ph-negative B-ALL patients. Building on these findings and to further refine risk-adapted treatmentstrategies, the ongoing GRAALL-2024 trial prospectively randomizes allo-HSCT in patients with pooroncogenic characteristics or EOI MRD response, but who achieve undetectable MRD after blinatumomab."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • IKZF1 • KMT2A

First results of the Phase III GIMEMA ALL2820 trial comparing ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adult ph+ acute lymphoblastic leukemia patients (ASH 2025) - "Compared to the GIMEMA LAL2116 trial, anincrease in MRD negativity and less relapses were observed. A chemo-free approach should be the newstandard for adult Ph+ ALL."

Clinical • IO biomarker • P3 data • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myocardial Infarction • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock • ABL1 • IKZF1