Blincyto (blinatumomab)

P2, N=52, Not yet recruiting, The First Affiliated Hospital of Soochow University

P2, N=220, Recruiting, Amgen | Trial completion date: Mar 2029 --> Jul 2028 | Trial primary completion date: Jan 2028 --> Jul 2028

Second-generation and third-generation TKIs further improved outcomes by targeting most imatinib-resistant mutations, with ponatinib-based regimens achieving deep molecular responses and long-term survival in most patients. Concurrently, immunotherapies like blinatumomab and CAR-T cells have enabled potent chemotherapy-free strategies, yielding high molecular response rates and challenging the necessity of allo-HSCT for all patients. Current evidence supports reserving allo-HSCT for high-risk patients, while those with sustained minimal residual disease (MRD) negativity may be cured with TKI and immunotherapy alone. Future progress hinges on optimizing combinations, integrating novel agents like asciminib and venetoclax, and leveraging MRD and genomic profiling for precision medicine.

P2/3, N=340, Not yet recruiting, Merck Sharp & Dohme LLC

P1, N=20, Active, not recruiting, OHSU Knight Cancer Institute | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027 | Recruiting --> Active, not recruiting

P2, N=101, Recruiting, The First Affiliated Hospital of Soochow University

P3, N=488, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Feb 2027

P2/3, N=87, Recruiting, Universita Degli Studi Di Milano Bicocca | Not yet recruiting --> Recruiting

Blinatumomab combined with dasatinib is well tolerated in pediatric Ph+ ALL, and the adverse events are manageable.

Introduction of tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 fusion protein has revolutionized frontline therapy, with successive generations of TKIs-from imatinib to dasatinib and most recently ponatinib-achieving progressively deeper and more durable molecular responses. Concurrently, the integration of immunotherapy, particularly blinatumomab, has enabled chemotherapy-sparing approaches further improving tolerability and efficacy...Treatment-free remission strategies following prolonged TKI maintenance in non-transplant patients, and the integration of chimeric antigen receptor (CAR) T-cell therapy as bridge, consolidation, or salvage, represent emerging frontiers. This review critically examines the contemporary role of allogeneic HCT in Ph+ ALL and provides a framework for transplant decision-making in the contemporary era of targeted and cellular immunotherapy.

Next-generation TCE platforms integrating conditional activation, cytokine payloads, and checkpoint modulation-deployed with biomarker-guided selection and TME-modulating combinations-represent a transformative therapeutic strategy. With tarlatamab's phase III survival benefit establishing clinical proof-of-concept, and pivotal trials underway for xaluritamig and next-generation agents, TCEs are positioned to become standard-of-care platform therapies in biomarker-defined solid tumours by 2028-2030.

CD22-targeted therapies, including CD22 CAR-T cells and Inotuzumab Ozogamicin, show promise as alternatives, although data in those patients is limited...Among these patients, 27.9% received blinatumomab, 58.1% received CD19 CAR-T cells, and 14% received both...Patients with extramedullary disease had worse remission rates, and those previously resistant to CD19-targeted therapy had shorter RFS. CD22-targeted therapies offer a potential option for patients progressing after CD19-targeted immunotherapy, but high relapse rates highlight the need for better strategies for lasting remission.