Posted: Tuesday, March 15, 2022
The treatment landscape surrounding high-risk acute myeloid leukemia (AML) expanded with the discovery of hypomethylating agents and the BCL2 inhibitor venetoclax. However, older patients with newly diagnosed AML still respond poorly to standard induction chemotherapy, and after disease progression on venetoclax with hypomethylating agents, there are few options for salvage therapy. Following a previous phase IB trial, Justin Watts, MD, of Sylvester Comprehensive Cancer Center, University of Miami, and colleagues published a subsequent analysis of the single-agent activity of the recombinant bispecific antibody APVO436 as a second-line therapy in Frontiers in Oncology.
“Limitations of venetoclax-based therapy have emerged,” stated the authors. “A combination of T-cell–redirecting bispecific antibody such as APVO436 with venetoclax or azacitidine may have clinical potential.”
The study included 14 elderly patients with relapsed or refractory AML or myelodysplastic syndrome (MDS). Of the eight patients with AML, two had previously failed to respond to treatment with hypomethylating agents, and six, to venetoclax plus hypomethylating agents. Of the six patients with MDS, five had failed to respond to treatment with hypomethylating agents, and one, to venetoclax plus hypomethylating agents.
The authors observed single-agent activity at doses of 0.1 mg/kg to 0.7 mg/kg in four (50%) of the patients with AML. Three experienced prolonged stable disease, with a time to disease progression ranging from 211 days to 238 days, and another patient achieved a complete response after 92 days, making a full hematologic recovery. At doses of 0.1 mg/kg to 0.8 mg/kg, three patients with MDS (50%) had stable disease, and an additional three (50%) had a marrow complete response. For the combined 14 patients, the median overall survival was 282 days. It was also reported that APVO436 activated patients’ T cells, which was indicated by lower counts of circulating CD123+CD34+ and CD33+CD34+ peripheral blasts.
Disclosure: For full disclosures of the study authors, visit frontiersin.org.