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

Upcoming treatments (EADV 2026) - "Cytokines are small, low-molecular-weight proteins (~5–25 kDa) that serve as critical chemical messengers for cell-to-cell communication within the immune system. Produced by a wide range of cells, including immune cells (such as T cells, B cells, macrophages, and natural killer cells) and non-immune cells (such as endothelial, fibroblast, and epithelial cells), they regulate immunity, inflammation, and hematopoiesis.Key Approved Monoclonal AntibodiesPembrolizumab (Keytruda): Blockade of the PD-1 immune checkpoint for multiple solid tumors including melanoma and non-small cell lung cancer.Trastuzumab (Herceptin): Targeting of the HER2 receptor in HER2-positive breast cancers.Lecanemab (Leqembi): Clearance of brain amyloid-beta plaques for early-stage Alzheimer's disease.Blinatumomab (Blincyto): Bispecific T-cell engager utilized for B-cell precursor acute lymphoblastic leukemia.Emerging Formats and Pipeline DrugsBispecific and Multispecific Antibodies: Engineered to..."

Acute Lymphocytic Leukemia • Alzheimer's Disease • Breast Cancer • Chronic Spontaneous Urticaria • CNS Disorders • Dermatology • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Leukemia • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Pruritus • Solid Tumor • Urticaria • HAVCR2 • HER-2 • LAG3 • TIGIT

Gastrointestinal Adverse Events of Bispecific Antibodies in Cancer: A Systematic Review and Proportional Meta-Analysis (ACG 2026) - "Sensitivity analyses excluding studies with an 8-week blinatumomab exposure window (27.2%, 95% CI 18.1-37.4%) and mixed CTCAE version reporting (24.2%, 95% CI 14.2-35.9%) were consistent with the primary result...GPRC5D-directed oral toxicity could not be assessed because no talquetamab trials met inclusion criteria... Eight trials enrolling 870 participants across five bispecific antibody target classes were included. Any-grade diarrhea incidence was 25.4% (95% CI 16.4-35.6%; prediction interval [PI] 5.4-53.7%; I²=82.3%; tau²=0.013). Grade 3-4 diarrhea incidence was 1.0% (95% CI 0.0-4.5%; PI 0.0-9.3%; k=4, N=564)."

Adverse events • Bispecific • Retrospective data • Review • Oncology • Solid Tumor

Successful Cytotoxic Chemotherapy-Free Bridging to Hematopoietic Stem Cell Transplantation With Dasatinib and Prednisolone/Blinatumomab for Relapsed Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. (PubMed, Pediatr Blood Cancer) - No abstract available

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

Outcome after first relapse post-immunochemotherapy in older adults with Philadelphia-negative B-cell acute lymphoblastic leukemia: A GRAALL study. (PubMed, Cancer) - P2 | "These results indicate that salvage regimen should be proposed in this context, allowing 50% of patients to achieve CR2 and have better survival."

Journal • Retrospective data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD22

Blinatumomab as the first-line induction for ANCA-associated rapidly progressive glomerulonephritis. (PubMed, RMD Open) - No abstract available

Journal • ANCA Vasculitis • Glomerulonephritis • Nephrology • Vasculitis

Prolonged molecular control during intermittent reduced-intensity blinatumomab maintenance in a transplant-ineligible patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia and IKZF1 deletion. (PubMed, Clin Transl Immunology) - "A 64-year-old man with Ph+ ALL harbouring a heterozygous IKZF1 deletion relapsed while receiving dasatinib, with emergence of an ABL1 E255K/V mutation...Intermittent reduced-intensity blinatumomab maintenance guided by serial MRD monitoring was feasible and associated with durable molecular control in a transplant-ineligible patient with high-risk Ph+ ALL. This strategy merits prospective evaluation."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1 • CD8 • IKZF1

T cell Engager treatment in systemic sclerosis (ACR Convergence 2026) - "In conclusion, blinatumomab-mediated B cell depletion appears to be a safe and highly effective induction strategy in severe SSc, leading to sustained clinical improvement and potential reversal of fibrosis. Larger controlled studies are warranted to confirm these findings and define optimal treatment regimens."

Fibrosis • Immunology • Infectious Disease • Scleroderma • Systemic Sclerosis

CD38+ NK/T cells define responsiveness to Bi-specific T cell engagers in high-risk MAD5+RPILD: a real-world study and immune surveillance analysis (ACR Convergence 2026) - "Blinatumomab is well-tolerated and shows potential in improving 1-year survival and lung radiology for high-risk MDA5+ RPILD. Sustained CD38hi NK/T cell expansion with high cytotoxic and dysfunctional gene expression serves as a key indicator of treatment failure and poor prognosis, guiding future personalized therapeutic stratifications."

Bispecific • Clinical • IO biomarker • Real-world • Real-world evidence • Dermatomyositis • Immunology • Infectious Disease • Inflammation • Interstitial Lung Disease • Myositis • Pneumonia • Pulmonary Disease • Respiratory Diseases • CD27 • CD8 • GZMB • GZMH • IFIH1 • IL7R • NKG7 • PRF1

Cd3-Engaging Bispecific Antibodies Convert Human Regulatory T Cells into Cytotoxic Effectors (IMS 2026) - P2 | "11 patients were treated with teclistamab plus daratumumab, lenalidomide, and dexamethasone (Tec-DRD, n = 11) in the ongoing MajesTEC-5 (HD10/DSMMXX) trial (NCT05695508); 6 patients recived standard-of-care DRD as controls (n=6)...Generalizability was tested in vitro using three BTCEs (teclistamab (BCMA×CD3), blinatumomab (CD19×CD3), glofitamab (CD20×CD3)) to redirect primary human Tregs towards BCMA+, CD19+, and CD20+ cell lines... Our findings uncover a novel mechanism where BTCEs actively convert suppressive Tregs into cytotoxic, pro-inflammatory effectors that contribute to antitumor activity. Multi-color flow cytometry validates these dynamics in patients, showing a shift toward activated, cytotoxic memory Tregs. We identified the BATF/JUNB axis and IMiD-mediated Helios destabilization as targetable regulators of this process, supporting rational combination regimens to enhance T-cell-redirecting immunotherapies."

Bispecific • IO biomarker • Hematological Malignancies • Multiple Myeloma • FOXP3 • GZMA • IKZF2 • IL2RA • JUNB • NKG7 • TBX21

Pediatric Patients with High-Risk B-Cell ALL in First Complete Remission May Benefit from Less Toxic Immunotherapy with Blinatumomab – Results from Randomized Controlled Phase 3 Trial AIEOP-BFM ALL 2017 (ASH 2023) - "After a 4-drug induction phase, and two weeks of consolidation treatment, patients were randomized to receive Bortezomib in addition to standard consolidation (not part of this report). Taken together, these results show for the first time in newly diagnosed pts with HR B ALL, the favorable toxicity profile previously reported with Blinatumomab in pediatric relapsed ALL (Locatelli F et al, JAMA 2021; Brown P et al, JAMA 2021). We have demonstrated that the toxicity profile of Blinatumomab is much more favorable as compared to the intensive chemotherapy approach using HR-blocks. If upcoming analyses of outcome data will show no inferiority of the EA, blinatumomab replacement of some of the intensive chemotherapy blocks will become the new standard of care for treatment if newly diagnosed patients with HR B-ALL."

Clinical • P3 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation • AFF1 • IKZF1 • KMT2A • TCF3

Frontline Blinatumomab and Ponatinib in Ph+ Acute Lymphoblastic Leukemia: A Single-Center Real-World Experience (SOHO 2026) - "Interventions: After steroid prephase, dasatinib bridging was used (1 month) prior to ponatinib, until access approval...CNS prophylaxis included intrathecal triplet therapy with methotrexate, cytarabine, and dexamethasone, with a planned total of 15 administrations during ponatinib maintenance...In the CML blast phase patient, IGHV qPCR was not available; due to persistent BCR::ABL positivity, his treatment was supplemented with chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), and he achieved a complete metabolic response and proceeded to transplant... Frontline blinatumomab plus ponatinib is a feasible chemotherapy-free strategy in Ph+ B-ALL, although limited by lack of first-line approval. Discordant MRD findings highlight the need for careful monitoring. Ongoing follow-up will determine durability of responses and whether allogeneic transplantation can be avoided in selected patients."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • IGH

Olverembatinib Combined With Blinatumomab in Patients With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome–Positive B-Cell Precursor Acute Lymphoblastic Leukemia (SOHO 2026) - P1 | "Olverembatinib plus blinatumomab shows promising activity in patients with R/R Ph+ BCP-ALL or CML-LBP, with encouraging response rates and MRD clearance, and is generally well tolerated. The data support further investigation of this chemotherapy-free approach. AEs: adverse events, ALL: acute lymphoblastic leukemia, CML-LBP: lymphoid-blast-phase chronic myeloid leukemia, CR: complete response, DLT: dose-limiting toxicity, R/R Ph+ BCP-ALL: relapsed/refractory Philadelphia chromosome–positive B-cell precursor ALL, MRD: measurable residual disease, TKI: tyrosine kinase inhibitor."

Clinical • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL. (PubMed, J Clin Oncol) - "ABL1 mutations were found in seven cases. The final analysis of the D-ALBA study shows that a chemotherapy-free induction/consolidation regimen on the basis of a targeted strategy (dasatinib) and immunotherapy (blinatumomab) is effective in inducing durable long-term hematologic and molecular responses in adult Ph+ ALL, paving the way for a new era in the management of these patients."

IO biomarker • Journal • Hematological Disorders • Transplantation • ABL1 • IKZF1

Efficacy and Toxicity of Frontline Ponatinib Plus Blinatumomab for Adult Ph+ ALL Patients of All Ages. Intermediate Analysis of the Gimema ALL2820 (ASH 2024) - "In the previous GIMEMA LAL2116 trial, we showed the effectiveness of a chemo-free approach based on dasatinib followed by blinatumomab (Foà et al, NEJM 2020), with long-term (median follow-up 53 months) overall survival (OS) and disease-free survival (DFS) of 80.7% and 75.8%, respectively (Foà et al, JCO 2023). The combination was overall well tolerated, with very few treatment discontinuations, also in the elderly, suggesting that a ponatinib dose adjustment according to age may prevent severe toxicities. Lastly, with the biology-driven transplant allocation only 12% of patients have been transplanted so far."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • ABL1 • IKZF1

Primary efficacy analysis of phase II study investigating tyrosine kinase inhibitor (TKI) and inotuzumab ozogamicin-based therapy for newly diagnosed Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (ASH 2025) - "Tyrosine kinase inhibitor (TKI) + blinatumomab regimenshave demonstrated high MR4 rates and favorable overall survival (OS); however, these regimens includeup to 5 courses of blinatumomab which is a continuous 28-day infusion (Kantarjian et al, JCO 2024; Foa etal, JCO 2024)...Eligibilitycriteria includes newly diagnosed Ph+ ALL, age ≥ 18, ECOG ≤2, CD22+ on ≥20% blasts, and no centralnervous system (CNS) disease.Schema 1 was as follows; Course (C) 1 was (28 days) dasatinib (DAS) 140mg daily, dexamethasone (dex)10mg/m2 D1-7 & D15-21, and InO 0.8mg/m2 D8, 0.5mg/m2 D15 and D22...If MR4 was not achieved by end of C2 (EOC2), DAS was switched to ponatinib(PON)...TKI + InO-based therapy for newly diagnosed pts with Ph+ ALL has an MR3+ rate of 81% within 2 coursesand 100% of pts achieved MR4 and/or NGS MRD- disease by EOC3. No cases of VOD were seen withSchema 2. Given the excellent rates of MR3+ with limited cycles of InO, further development of thisinduction approach is..."

Clinical • P2 data • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Pulmonary Disease • Respiratory Diseases • Septic Shock • IKZF1

Comparison between Dasatinib-Blinatumomab Vs Ponatinib-Blinatumomab Chemo-Free Strategy for Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia Patients. Preliminary Results of the Gimema ALLL2820 Trial (ASH 2023) - "So far, the benefit of the current protocol appears to rely on a lower relapse rate, with only 1 relapse being observed to date, while in the same time period 3 relapses were documented with the dasatinib-blinatumomab combination. Further details will be provided."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • CD19 • IKZF1

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

Mini-hyper-CVD with venetoclax (Ven) for patients with relapsed/refractory (R/R) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL): A phase II study. (ASCO 2023) - P1/2 | " Pts ≥18 years with R/R Ph-negative B- or T-cell ALL received mini-HCVD alternating with methotrexate and cytarabine for up to 8 cycles...Rituximab (if CD20+ B-ALL) and prophylactic IT chemotherapy x8 doses were given for the first 4 cycles. Pts with T-ALL received additional 2 cycles of nelarabine and peg-asparaginase during consolidation without Ven, and 2 cycles during maintenance. Maintenance with vincristine, prednisone and Ven was given for up to 2 years...Among the 18 B-ALL pts, 16 (89%) had received prior blinatumomab and 7 (39%) prior inotuzumab... The combination of low-intensity chemotherapy mini-HCVD with Ven in pts with R/R Ph-negative ALL was well-tolerated and resulted in a response rate of 67%. Further studies examining the role of Ven-based therapies in ALL are needed for newly diagnosed and R/R pts. Clinical trial information: NCT03808610."

Clinical • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • Transplantation • CD20

Olverembatinib-Based Treatment for Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Multi-Center Retrospective Study (SOHO 2026) - "Blinatumomab was applied for consolidation in 9 of 18 patients (50%). Nine of 18 (50%) patients have entered the maintenance therapy phase, of whom 6 received olverembatinib only, 2 received a combination of olverembatinib and chemotherapy, and 1 received a combination of dasatinib and chemotherapy due to financial issues... Olverembatinib-based regimen with lower-intensity chemotherapy showed promising outcomes with acceptable side effects as frontline therapy in patients with Ph+ ALL, warranting further trials to investigate better strategies. ALL: acute lymphoblastic leukemia, allo-HSCT: allogeneic hematopoietic stem cell transplantation, BCR::ABL1: breakpoint cluster region–Abelson murine leukemia viral oncogene homolog 1 fusion, CAR-T: chimeric antigen receptor T-cell, CMR: complete molecular remission, CR: complete response, IKZF1: Ikaros family zinc finger protein 1, PCR: polymerase chain reaction, Ph+: Philadelphia chromosome–positive, TKI: tyrosine kinase..."

Retrospective data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • IKZF1

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

Randomized comparison of ponatinib versus imatinib in combination with chemotherapy in patients 55 years of age and older with newly diagnosed ph+ ALL: Molecular response and initial outcome analysis of the EWALL PH03 Study (ASH 2025) - P2 | "Moreover, the bispecific T-cell engager blinatumomab (BLIN) hasemerged as a potent front-line modality in Ph+ALL. In older pts with Ph+ALL receiving upfront reduced-intensity chemotherapy (EWALL), PONinduces a higher, albeit not significant, deep molecular response rate compared to IM, The safety profileof PON was consistent with known AEs and did not lead to a higher rate of withdrawals from studytreatment than IM. The impact on survival will require longer follow-up."

Clinical • Combination therapy • Acute Lymphocytic Leukemia • Hypertension • Pancreatitis • Thrombosis • ABL1 • BCR

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) yields durable remissions and survival in adults with newly diagnosed acute lymphoblastic leukemia/lymphoma (ALL): Long-term follow-up of a prospective trial (ASH 2025) - P2 | "In a single-arm Phase II trial weconducted, DA-EPOCH ± rituximab (R) ± TKI yielded comparable morphologic (morph) and measurableresidual disease (MRD)- remissions with less toxicity than seen in a comparable cohort of patientsreceiving hyperCVAD. This study completed accrual in 2021, before routine upfront incorporation ofimmunotherapy and ponatinib (if Ph+)...Imatinib or dasatinib was added if Ph+, and R if CD20+...8 pts (15%) switched to blinatumomab whenMRD+ after DA-EPOCH, with none receiving it when MRD-. DA-EPOCH±R±TKI yields durable remissions, with survival comparable toimmunotherapy-based strategies for ALL... DA-EPOCH±R±TKI yields durable remissions, with survival comparable toimmunotherapy-based strategies for ALL. Unlike many other approaches, outcomes for older pts weresimilar to the general study population. These results support DA-EPOCH±R±TKI as a curative-intentoption, particularly in resource-limited settings."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • ABL1 • CD20

Blinatumomab in Combination with Immune Checkpoint Inhibitors (ICIs) of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Results of a Phase I Study (ASH 2023) - "We describe results of a multi-center phase I study combining blina with immune checkpoint inhibitors (ICIs) targeting PD-1 (nivolumab) +/- CTLA-4 (ipilimumab). Combination therapy with blina and ICIs in R/R ALL is safe, feasible, and associated with a high MRD-negative response rate. Long-term survival was promising in comparison to prior results with blina monotherapy, especially following consolidation with alloBMT. A randomized trial of blina +/- nivolumab is needed to confirm the benefit of this combination."

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Endocrine Disorders • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Hypotension • Immunology • Neutropenia • Pneumonia • PD-L1

Cutaneous Toxicity of the Dasatinib-Blinatumomab Combination: A Case Report of an Acneiform Eruption (EADV 2026) - No abstract available

Case report • Clinical • Dermatology

A Phase I Study of Asciminib (ABL001) in Combination with Dasatinib and Prednisone for BCR-ABL1-Positive ALL and Blast Phase CML in Adults (ASH 2023) - P1 | "Both patients with imatinib-refractory CML-LBC progressed (C9, C3). Of those with ALL, 8 bridged to SCT after 2-8 cycles; 2 elected local care (C5, C7); 1 transitioned to ponatinib for inadequate response plus recurrent DAS pulmonary toxicity (C4); 6 remained on study treatment until disease progression (C4 – MRD+, C45, C11, C11); 3 remain on study... Dual ABL1 kinase inhibition with ASC and DAS plus pred in BCR::ABL1+ ALL and CML-LBC is feasible and tolerable in adults with BCR::ABL1+ ALL and CML-LBC. DLTs at ASC 160 mg/d were asymptomatic amylase and lipase elevation, without clinical sequelae. ASC 80 mg/day was declared the RP2D, and an expansion cohort of 10 pts was completed."

Clinical • Combination therapy • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • Pancreatitis • ABL1 • BCR