Blincyto (blinatumomab)

This review summarizes recent advances in the application of low-intensity chemotherapy, CD19/CD22-targeting antibodies such as blinatumomab and inotuzumab ozogamicin, the BCL-2 inhibitor venetoclax, and chimeric antigen receptor (CAR) T-cell therapy for elderly pH⁻ B-ALL patients. Clinical studies indicate that these strategies can increase remission rates and survival while reducing treatment-related toxicity, offering particular benefit to older patients who are unsuitable for intensive chemotherapy. Future efforts should focus on optimizing combination and sequential regimens, as well as personalizing treatment approaches to further improve efficacy and safety.

CD19-directed CAR-T-cell therapy and bispecific antibodies (e.g., blinatumomab) have demonstrated high remission rates in early-phase clinical trials...Their integration into standard protocols, especially for high-risk and relapsed patients, is crucial to enhancing long-term outcomes. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251110522, identifier CRD420251110522.

Targeted therapies, such as tyrosine kinase inhibitors for Philadelphia chromosome-positive ALL, Chimeric Antigen Receptor T cell therapy for relapsed or refractory cases, and monoclonal antibodies like blinatumomab and inotuzumab ozogamicin, have transformed treatment outcomes while reducing chemotherapy-related toxicity. Despite these advances, challenges remain, including the development of therapy resistance (e.g., BCR-ABL1 and FLT3 mutations) and long-term adverse effects such as cardiotoxicity and secondary malignancies. This narrative review summarizes recent innovations in risk assessment and targeted therapies, highlights current challenges, and discusses future directions to optimize personalized pediatric leukemia care.

P3, N=304, Recruiting, Amgen | Trial completion date: Sep 2031 --> Jul 2031

P=N/A, N=50, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China | Initiation date: Sep 2025 --> Jun 2026

Although mAbs such as rituximab are primarily used in adults, the other modalities have demonstrated efficacy in both pediatric and adult patients with B-ALL. Among ADCs, inotuzumab ozogamicin (InO) has proven effective as monotherapy for relapsed disease, leading to FDA approval for patients aged >1 year with relapsed/refractory B-ALL...T-cell-engaging antibodies are now a standard component of therapy for most patients with newly diagnosed and relapsed B-ALL, following the successful integration of the bispecific T-cell-engager blinatumomab into chemotherapy regimens for both adults and children...Overall, immune-based therapies are now a mainstay of B-ALL therapy. This article reviews the efficacy and safety data of several immune-based therapies in B-ALL and discusses a number of outstanding questions and possible future directions for the use of immune-based approaches in the treatment of B-ALL.

P2/3, N=1200, Recruiting, Assistance Publique - Hôpitaux de Paris | Not yet recruiting --> Recruiting

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