Lintuzumab-Ac225 plus CLAG-M yielded “deep and meaningful responses” in patients with relapsed/refractory acute myeloid leukemia (AML), according the results of a phase 1 study published in Leukemia.
The study was led by Sameem Abedin, MD, an associate professor of medicine (hematology and oncology) at the Medical College of Wisconsin.
Lintuzumab-Ac255 is a humanized anti-CD33 antibody linked to Actinium-225 delivering high-energy alpha-particles to leukemia cells, inciting double-strand DNA breaks and cell death, according to the study investigators.
The study is the first to evaluate the safety and tolerability of combining a radioimmunotherapy agent, lintuzumab-Ac225, in combination with intensive chemotherapy for AML.
Lintuzumab-Ac225 plus CLAG-M ‘well tolerated’
In terms of safety, the results showed that lintuzumab-Ac225 plus CLAG-M was well tolerated overall. The investigators did not observe any significant hepatic or renal toxicities, and they reported that the most common grade 3/4 treatment-emergent adverse events were hematologic.
Blood radioactivity measurements indicated that lintuzumab-Ac225 is rapidly cleared after administration, Dr. Abedin and colleagues noted.
In terms of efficacy, the composite complete remission (CRc) rate (CR/CRi) for the 23 evaluable patients was 56.5% and was 62.5% at the recommended phase 2 dose of 0.75 µCi/kg lintuzumab-Ac225. The overall response rate (ORR) was 65.2% for all patients, and 75% at the RP2D. Among 14 patients who received 1 or 2 prior lines of therapy before enrollment, the CRc rate was 79%. In the 20 patients with high-risk AML, the CRc rate was 50% and the ORR was 60%.
In terms of survival, among all enrolled patients (n=26), the estimated two-year overall survival was 23.1% (95% CI, 9.4–40.3) and the estimated one-year progression-free survival was 30.8% (95% CI, 14.6–48.5).
“Lintuzumab-Ac225 in combination with CLAG-M had a tolerable safety profile with manageable toxicities and demonstrated promising efficacy in patients with R/R AML, including high-risk patient subgroups such as those with TP53 alterations and prior venetoclax exposure,” the investigators wrote. “These phase 1 results provide reasonable rationale evidence to further investigate efficacy and survival with lintuzumab-Ac225 following CLAG-M in patients with R/R AML.”
Reference
Abedin SM, Guru Murthy GS, Hamadani M, et al. Phase 1 study of lintuzumab-Ac225 combined with CLAG-M salvage therapy in relapsed/refractory acute myeloid leukemia. Leukemia. Published online February 15, 2025. doi:10.1038/s41375-025-02528-3
