Blincyto (blinatumomab)

Consistent with prior preclinical studies, we demonstrate that dasatinib and ponatinib, unlike SRC sparing TKIs (imatinib, nilotinib), antagonize blinatumomab's T-cell engaging efficacy by potently inhibiting LCK Y394 phosphorylation, a critical step in proximal TCR signaling. We show that TKI-induced T-cell suppression and antagonism can be significantly improved by supplementing co-cultures with common gamma-chain cytokines, particularly IL-7. IL-7 robustly enhances human T-cell proliferation, reduces exhaustion, and significantly improves blinatumomab's cytotoxic efficacy in the presence of Src/BCRABL1 TKIs.

P1/2, N=50, Not yet recruiting, Novartis Pharmaceuticals

Successive generations of TKIs have transformed Ph + ALL from a uniformly fatal leukemia into a highly treatable disease, with dasatinib or ponatinib-based and TKI-blinatumomab regimens achieving high rates of complete molecular remission...Novel agents, including asciminib and olverembatinib, are expanding options for resistant or relapsed disease, while CAR-T cell therapy and next-generation bispecific T-cell engagers are emerging as promising tools for refractory and post-TKI settings...Integrating potent TKIs with immunotherapy enables deep and durable remissions, potentially eliminating the need for upfront transplantation in selected patients. Future research should define molecular predictors of treatment-free remission, optimize CNS prophylaxis in targeted regimens, and establish standardized monitoring for safe TKI discontinuation.

Supportive care included epoetin alfa, romiplostim, iron, and vitamin supplementation. CONCLUSIONS This is the first known reported case that demonstrates the feasibility and effectiveness of a chemotherapy-free induction strategy using inotuzumab and blinatumomab for frontline treatment of Ph-negative B-ALL in Jehovah's Witness patients. It shows that MRD negativity can be safely achieved without cytotoxic chemotherapy or transfusion support and supports the use of the ALLIANCE A041703 trial regimen as a treatment model for this unique and underserved patient group.

P2, N=146, Not yet recruiting, The Second Affiliated Hospital of the Army Medical University; The Second Affiliated Hospital of the Army Medical University

This review highlights the evidence defining its poor prognosis, which is primarily driven by profound chemoresistance to conventional therapies, including glucocorticoids. Finally, we discuss the rapidly evolving therapeutic landscape, detailing the limitations of standard intensive chemotherapy and the immense promise of novel targeted strategies, such as Menin inhibitors (e.g., Revumenib), DOT1L inhibitors, and immunotherapies (e.g., CAR-T cells, Blinatumomab), which hold the potential to revolutionize outcomes for this high-risk leukemia subtype.

Novel agents under development include the subcutaneous (SC) form of blinatumomab, which has demonstrated efficacy even in patients with prior blinatumomab exposure. Altogether, these developments frame the next set of questions in ALL, which will be addressed in this review.

We furthermore discuss genetically engineered CD38 knock-out multitarget natural killer cells, expressing anti-B cell maturation antigen (BCMA) CAR, IL-15RF and hnCD16, administered in combination with daratumumab (anti-CD38) in this context...Likewise, we hypothesize the use of bi-specific T cell engagers such as CD19 blinatumomab or BCMA teclistamab for the treatment of AMR...In summary, anti-CD38 antibodies currently constitute the drug class with the strongest evidence for AMR treatment. To date, most CD38 antibodies have been shown to be safe, even after several years of administration in patients with multiple myeloma.

Patients remaining on dasatinib maintained elevated NK cells with a more mature phenotype, suggesting a durable effect. These results highlight the greater dasa+blina immune activation, supporting a potential synergistic effect of the drug combination.

Multivariate analysis identified Day 1 concurrent IT administration as an independent risk factor (OR = 12.5; 95% CI: 1.45-131; p = 0.023). Initiating IT chemotherapy on the same day as blinatumomab infusion significantly increases the risk of neurotoxicity in pediatric ALL patients.

P2, N=64, Suspended, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

P2, N=55, Enrolling by invitation, SWOG Cancer Research Network | Not yet recruiting --> Enrolling by invitation