Promising Results with Targeted Combination Therapy for patients with new diagnoses of Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) accounts for approximately one-third of the new cases of leukemia in the United States and has already caused over 11,500 deaths in 2022¹. The past several years have brought few significant advances in AML treatment. Fortunately for patients with AML (and their providers) there are promising new therapies on the horizon. Several are nearing approval from the Food and Drug Administration (FDA). These innovations are expected to impact patient outcomes, especially for patients with refractory/relapsed AML, and those with mutation that make standard therapeutic options ineffective.

Researchers from the Roswell Park Comprehensive Cancer Center are making significant contributions toward expanding treatment options for patients with AML who have complex mutations. A recently completed investigation was led by Eunice Wang, MD, Chief of Leukemia services and Medical Director of Infusion services at the Roswell Park Comprehensive Center. Her team led an international phase III study to test the safety, tolerability, and effectiveness of gilteritinib (GIL) plus azacitidine (AZA) chemotherapy in patients with newly diagnosed AML who have mutations in the FMS-like tyrosine kinase 3 (FLT3) gene andareunable to receive intensive induction chemotherapy (IIC). Dr. Wang joined the faculty at Roswell Park in 2003 and has since become a national leader in the development and implementation of early-stage clinical trials for acute leukemias (AML, ALL) and myeloproliferative disorders.

The study included 123 patients with a median age of 78 years who were randomized to receive either GIL+AZA treatment or AZA alone. Results demonstrated significantly higher composite complete remission rates for patients who receivedGIL+AZA vs AZA alone (58.1 vs 26.5%). Importantly, patients randomized to GIL + AZA tolerated the drug well with few side effects. GIL has previously been shown to be safe and efficacious in patients with AML relapse. This study demonstrates the extension of promising findings to patients with new diagnoses.

This study is important because approximately one-thirdof patients with AML present with the FLT3 gene mutation. This mutation is associated with a worse prognosis and aggressive clinical disease that tends to relapse, underscoring the need for effective treatment options for these patients. Survival is poor, and treatment options are limited for patients in this group. The study demonstrates that GIL+AZA could prolong and improve the quality of life for older AML patients who are unable to receive intensive induction chemotherapy. Dr. Wang and the rest of the investigative team at the Roswell Park Comprehensive Cancer Center intend to study other GIL combination regimens and are simultaneously creating trials to assess the value of outpatient oral treatment options for patients with leukemia. This leadership is in keeping with Roswell Park’s long history of innovation in leukemia management including developing some of the first FLT3 inhibitors used in patients with AML.