We validated these clinical and molecular findings in an independent validation cohort of 302 NPM1 mut patients enrolled in the acute myeloid leukemia study group (AMLSG) 09-09 clinical trial, which included the administration of all-trans retinoic acid (ATRA) to all patients and a randomization for gemtuzumab ozogamicin. In this cohort, the APL-like immunophenotype was associated with events occurring within the first 15 days but did not influence mortality, likely due to protocol-driven patient selection. Our findings have important clinical implications that warrant the development of studies exploring disease-tailored clinical measures to mitigate the risk of early vascular events, as in current APL management.

P3, N=700, Active, not recruiting, University of Birmingham | Recruiting --> Active, not recruiting

Such inhibition caused cell line-dependent changes in the expression of apoptotic regulators, including BCL-2, MCL-1 and p53 protein, suggesting that cellular context shapes responses to combined treatments. In conclusion, our findings identify BCL-2 and PI3K inhibition as a promising new approach to sensitize AML cells to GO therapy, and highlight the importance of these pathways in determining the cellular response to gemtuzumab ozogamicin.

P1, N=35, Recruiting, Bristol-Myers Squibb Services Unlimited Company | Not yet recruiting --> Recruiting

P=N/A, N=165, Recruiting, Pfizer | Trial completion date: Apr 2027 --> Jul 2027 | Trial primary completion date: Apr 2027 --> Jul 2027

P2/3, N=216, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | N=80 --> 216 | Initiation date: Dec 2025 --> Mar 2026

P1, N=32, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Dec 2025 --> Dec 2027

P2, N=162, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Feb 2026 --> Jun 2026

P1, N=35, Not yet recruiting, Bristol-Myers Squibb Services Unlimited Company

In the in vivo experiments, mice bearing Molm13-Luciferase tumor cells were assigned to different treatment groups and were administered with saline, Gemtuzumab-MMAE, or Clone3HM-MMAE...Clone3HM-MMAE, in particular, demonstrated excellent anti-tumor activity along with a strong safety profile. These results strongly support the further development of targeted therapeutic strategies for AML.

P2, N=19, Active, not recruiting, Centre Antoine Lacassagne | Recruiting --> Active, not recruiting | N=50 --> 19 | Trial completion date: Mar 2027 --> Jul 2028 | Trial primary completion date: Mar 2027 --> Jul 2028

Twenty-five years ago, the FDA gave the first approval to an antibody-drug conjugate (ADC), the CD33-targeting gemtuzumab ozogamicin for acute myeloid leukemia. As the drug faced setbacks and redemption-it was withdrawn in 2010 following poor phase III trial results but reapproved in 2017 at a lower dose-a surge of pharmaceutical interest in ADCs has yielded newly approved agents and new strategies for developing them.