CPX-351 plus gemtuzumab ozogamicin in relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome.

Outcomes of patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and those with myelodysplastic syndrome (MDS) with increased blasts (IB) who progress after therapy with hypomethylating agents (HMA) are dismal, especially when without targetable genetic aberrations. In this phase 2 pilot trial, we treated 50 patients (48 with R/R AML and 2 with post-HMA MDS-IB) with a combination of CPX-351 and gemtuzumab ozogamicin (GO). The median age of patients was 68.7 years (range, 21.5-76.8). Among patients with AML, 87% had received prior HMA, 83% prior venetoclax, 65% prior chemotherapy, and 15% had undergone hematopoietic stem cell transplantation (HSCT). Both patients with MDS had received HMA and venetoclax previously. A composite complete remission (CR; CRc; CR + CR with incomplete count recovery) was achieved in 9 patients (19%) with AML, 2 of whom were consolidated with HSCT, and 1 of the 2 patients with MDS achieved marrow CR with incomplete platelet recovery. The median event-free survival and overall survival (OS) for the entire group were 1.7 and 5.7 months, respectively, whereas in responders they were 6.1 and 9.3 months, respectively. Among patients with AML who achieved a CRc, the 1-year OS rate was 56%. Overall, 45 patients (90%) had a grade ≥3 adverse event (AE), with infections being the most common AE, and there were no AEs of hepatic sinusoidal obstruction syndrome. The combination of CPX-351 + GO is feasible and led to a CRc rate of 19% in patients with R/R AML but with limited duration of responses and low rates of subsequent HSCT. This trial was registered at www.clinicaltrials.gov as NCT03672539.