Besponsa (inotuzumab ozogamicin)

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.

P2, N=5, Terminated, St. Jude Children's Research Hospital | N=32 --> 5 | Trial completion date: Dec 2031 --> Sep 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2029 --> Sep 2025; Closed due to slow accrual

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.

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.

P1, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial completion date: Jun 2026 --> Dec 2026

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

These results support further evaluation of combination therapies with corresponding small-molecule inhibitors (currently pursued for therapy of other cancers) toward clinical testing as novel strategies to increase the efficacy of CLM-based ADCs such as GO and InO.

This study analyzed 24 R/R ALL patients receiving tisagenlecleucel after BT (Inotuzumab [n=10] vs. chemotherapy/steroids [n=14]). Overall, inotuzumab as BT effectively reduces tumor burden but attenuates CAR-T expansion without compromising survival outcomes. As high tumor burden is a dominant driver of relapse and toxicity, the net effect of inotuzumab may be favorable in selected patients.

P2, N=31, Active, not recruiting, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Active, not recruiting | N=55 --> 31 | Trial completion date: Dec 2025 --> Nov 2030

P1/2, N=276, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

Bispecific antibodies such as blinatumomab (anti-CD19), antibody-drug conjugates like inotuzumab ozogamicin (anti-CD22), and monoclonal antibodies such as daratumumab (anti-CD38) have demonstrated efficacy in relapsed or refractory disease with improved safety profiles. The integration of targeted and immune-based therapies into conventional regimens represents a decisive step toward precision medicine, aiming to enhance survival outcomes while reducing treatment-related toxicity and improving quality of life in ALL children. This review aims to provide a comprehensive overview of the current understanding of ALL pathobiology and therapeutic approaches, with particular emphasis on the expanding role of immunotherapeutic strategies in pediatric disease.

Blinatumomab and inotuzumab ozogamicin have become established treatments, enhancing remission rates, measurable residual disease clearance, and overall survival in relapsed/refractory disease, and these agents, are now increasingly incorporated into frontline therapy...In acute myeloid leukemia (AML), gemtuzumab ozogamicin has shown significant clinical benefits, particularly in molecularly defined subsets...This review highlights how immunotherapy has reshaped treatment paradigms across acute leukemias, underscoring successful experiences in B-ALL. These insights emphasize the need for continued innovation to overcome existing hurdles in AML and T-ALL, ultimately aiming to enhance patient outcomes and quality of life.