CPX-351 (liposomal daunorubicin/cytarabine) + CD33-targeted gemtuzumab ozogamicin delivers 19% CRc in heavily pretreated R/R AML

CPX-351, a fixed-ratio liposomal formulation of daunorubicin + cytarabine, was combined with gemtuzumab ozogamicin (GO), a CD33-directed calicheamicin antibody–drug conjugate, in a Phase 2 pilot study in relapsed/refractory AML and post-HMA MDS with increased blasts (n=50; AML n=48, MDS-IB n=2; median age 68.7 years; NCT03672539). In the AML cohort—87% prior HMA, 83% prior venetoclax, 65% prior chemotherapy, 15% prior HSCT—composite CR (CRc=CR+CRi) was 19% (9/48); in MDS-IB, 1/2 achieved marrow CR with incomplete platelet recovery, and only 2 AML responders proceeded to HSCT; median EFS/OS were 1.7/5.7 months overall vs 6.1/9.3 months in responders, and among AML patients achieving CRc the 1-year OS rate was 56%. Grade ≥3 AEs occurred in 90% (45/50), infections were most common, and notably there were no hepatic sinusoidal obstruction syndrome events; efficacy appears in the same ballpark as (or below) typical intensive salvage chemotherapy and post–HMA/venetoclax failure salvage outcomes, which remain poor overall and are largely defined by whether patients can be bridged to transplant.