At Roswell Park Comprehensive Cancer Center in Buffalo, patients with a particularly stubborn form of leukemia are experiencing something rare: deep remissions achieved in weeks. Researchers there have co-led a study showing that a three-drug combination—ziftomenib paired with venetoclax and azacitidine—delivers strong responses in people with NPM1-mutated acute myeloid leukemia (AML) whose disease has returned or resisted standard treatment.
NPM1-mutated AML is notoriously difficult to manage once initial therapies stop working. This is why the results published in the journal Blood matter so much: they offer new hope for patients facing a form of cancer with severely limited options. The study emerged from an international clinical trial examining whether ziftomenib, an oral targeted therapy branded as Komzifti and already approved as a single-agent treatment by the U.S. Food and Drug Administration, could amplify results when combined with two established drugs.
The numbers tell a compelling story. Among patients who had not previously received venetoclax, nearly 90% responded to the three-drug combination, with 70% achieving a complete or near-complete remission. Many of these responses were extraordinarily deep—meaning no measurable cancer cells remained when tested with highly sensitive detection methods. Even in patients who had already tried venetoclax, about half still responded. What made these results particularly striking was their speed: responses typically emerged within about four weeks on average, and many persisted for several months.
"These results are highly encouraging, particularly in the context of an aggressive leukemia for which limited treatment options exist," said Dr. Eunice Wang, Chief of Leukemia at Roswell Park and first author of the study. "We observed deep and durable responses with this three-drug combination, along with a safety profile that supports continued study." Safety emerged as another key advantage. The treatment was generally well tolerated, with low rates of serious side effects—a crucial consideration when treating patients with already-advanced disease.
The findings come from the ongoing phase 1a/b KOMET-007 clinical trial. While ziftomenib's single-agent approval represented progress, its use in combination therapy remains investigational, meaning this research opens a genuinely new frontier. Roswell Park's patients were among the first globally to access ziftomenib through the institution's Early Phase Leukemia Clinical Trials program, supported by the Roswell Park Alliance Foundation. The center is also contributing to additional research examining ziftomenib combinations in newly diagnosed AML patients, with results to be presented at the 2026 European Hematology Association Congress later this month.
For leukemia patients and their families, the arc of this research reflects something essential: targeted therapies tailored to specific genetic mutations, combined thoughtfully with proven agents, can fundamentally shift what's possible. The study suggests that NPM1-mutated AML, once a diagnosis carrying severely constrained options, may soon offer multiple pathways to remission. As these findings move deeper into development, they signal that precision medicine continues to reshape what doctors can offer patients facing some of oncology's toughest challenges.