Mylotarg (gemtuzumab ozogamicin)

This review compared the efficacy and safety of low-dose cytarabine (LDAC), azacitidine (AZA), 5- and 10-day decitabine (DEC), and gemtuzumab ozogamicin, alone or combined with drugs such as venetoclax (VEN), in older adults with AML ineligible for conventional chemotherapy. Treatment decisions should consider patient goals and functional status. These findings informed eight recommendations in updated ASH-AML guidelines.

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.

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 As the drug faced setbacks and redemption-it was withdrawn in 2010 following poor phase III trial results but reapproved in 2017 at a lower dose-a surge of pharmaceutical interest in ADCs has yielded newly approved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.

Our results show that GO can safely be combined with intensive chemotherapy with midostaurin in ND, FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT03900949.

P2, N=151, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P2, N=162, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2028 --> Nov 2027 | Initiation date: Nov 2025 --> Feb 2026 | Trial primary completion date: Jul 2028 --> Nov 2027

P1, N=18, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2025 --> Apr 2027 | Trial primary completion date: Nov 2025 --> Apr 2027

P2, N=70, Suspended, St. Jude Children's Research Hospital | Recruiting --> Suspended

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.

P3, N=1186, Recruiting, Children's Oncology Group | Trial completion date: Sep 2027 --> Jun 2029 | Trial primary completion date: Sep 2027 --> Jun 2029

The anti-CCRL2 ADC demonstrated strong CCRL2-selective cytotoxicity against cell lines derived from MDS/AML patients with TP53 mutations and erythroid features, surpassing the cytotoxic effects observed with gemtuzumab and PBD-conjugated anti-CD33 and anti-CD123 ADCs...This agent also suppressed the leukemic growth of TP53- mutated MDS/AML cell line xenografts, improving mice survival and decreasing the leukemic burden in patient-derived TP53 -mutated MDS/AML xenografts. In conclusion, our study introduces CCRL2 as a potential new therapeutic target in high-risk MDS/AML.