Blincyto (blinatumomab)

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.

P1, N=26, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: May 2027 --> Jun 2028 | Trial primary completion date: May 2027 --> Jun 2028

P2, N=19, Completed, University of California, Davis | Recruiting --> Completed | Trial primary completion date: Feb 2025 --> Jul 2025

P2, N=20, Recruiting, Northside Hospital, Inc. | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Nov 2025 --> Nov 2026

P2, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

P1/2, N=100, Recruiting, Cardiff University | Not yet recruiting --> Recruiting

An example of this is blinatumomab, an FDA-approved BiTE structure for the treatment of B-cell acute lymphoblastic leukemia (B-ALL)...Ultimately, we present two promising TCR-BiTEs that are specific to two different HLAs (HLA:03:01 and HLA:11:01) targeting KRAS G12V, serving as valuable starting points for further evaluation and design in vitro. We validated the design of our TCR-BiTE structures through AlphaFold tools, free energy estimation methods, and molecular dynamics analysis, thereby also providing a potential computational pipeline that can be applied in the design of TCR-BiTE structures targeting other mutations in addition to KRAS G12V.

P2, N=222, Recruiting, National Cancer Institute (NCI) | Phase classification: P3 --> P2

P3, N=348, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=84, Recruiting, National Cancer Institute (NCI) | N=64 --> 84