Besponsa (inotuzumab ozogamicin)

P4, N=44, Completed, Pfizer | Active, not recruiting --> Completed

CD24 therefore emerged as an effective target in BCP-ALL, and the combination of CD24 and CD123 as a potential effective double-targeting strategy. The combination of different recognition modalities (eg, a CAR and CD16) should be tested to determine whether it provides synergistic cytotoxic activity in triple targeting.

Patients ≥60 years with Ph-negative B-cell ALL and TP53 VAF ≥45% had poor outcomes, with 4-year event-free survival (EFS) and overall survival (OS) of 28%, driven primarily by increased relapse risk, even among patients treated with frontline inotuzumab ozogamicin (INO) and/or blinatumomab. TP53 persistence at remission occurred in 44% of tested patients and was associated with increased ALL relapse risk. These results demonstrate that TP53 VAF is prognostic in older patients with Ph-negative B-cell ALL; high VAF may increase relapse risk but is not independently associated with survival in younger patients.

P2, N=80, Recruiting, Children's Oncology Group | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026

P2, N=42, Recruiting, Sheng-Li Xue, MD | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

P=N/A, N=102, Active, not recruiting, Ruijin Hospital

Recent advances in immunotherapy, including blinatumomab, inotuzumab ozogamicin, and CD19-directed CAR T-cell therapy, have shown significant efficacy and favorable tolerability in pediatric and adult DS-ALL. Emerging approaches incorporating early immunotherapy, MRD-guided treatment, and chemotherapy-free regimens may improve survival and quality of life. Prospective DS-specific trials are essential to optimize therapy and close the outcome gap in this high-risk population.

Further randomized studies are needed to validate these findings. https://www.crd.york.ac.uk/prospero/, identifier CRD42024619042.

P2, N=55, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | N=31 --> 55

With the advent of targeted therapies, including antibodies such as blinatumomab and inotuzumab and small molecule inhibitors, such as the BCR::ABL1 tyrosine kinase inhibitors, Bruton tyrosine kinase inhibitors, and venetoclax, the treatment landscape of leukemia has drastically changed, improving survival outcomes while relying less on overall chemotherapy intensity in many leukemia types. Advancements in the treatment of TP53-mutated, MECOM-rearranged, and treated secondary AML are still needed to improve outcomes in these adverse risk groups. The authors also review the recent progress in the treatment of the acute and chronic leukemias.

Targeted immune therapies like blinatumomab, inotuzumab ozogamicin (InO), rituximab, and nelarabine are being combined with traditional chemotherapy protocols to enhance remission rates and minimal residual disease (MRD) negativity while decreasing toxicities...Ph + ALL patients receive standard treatment with multi-agent chemotherapy and TKIs dasatinib or ponatinib and blinatumomab as part of their frontline therapy to enhance molecular responses and minimize the requirement for allogeneic hematopoietic stem cell transplantation (allo-HCT)...The practice of testing MRD and genomic profiling at diagnosis revolutionized treatment approaches by allowing personalized curative strategies for all patients. Research on clinical trials aims to establish the best sequence of targeted therapies and CAR T-cell therapy for high-risk and MRD-positive patients to achieve longer survival rates with reduced toxicity and less dependence on allo-HCT in first remission.

P2, N=15, Terminated, M.D. Anderson Cancer Center | N=44 --> 15 | Trial completion date: Mar 2027 --> Oct 2025 | Recruiting --> Terminated | Trial primary completion date: Mar 2027 --> Oct 2025; <75% participation