New Therapy for FLT3-Mutated Acute Myeloid Leukemia FLT3 is a gene that encodes a signaling protein (a tyrosine kinase) required for the normal devel- opment of blood cells. It is also mutated in approx- imately 30 percent of newly diagnosed acute myeloid leukemias (AML) in adults, and patients with FLT3-mutated AML have particularly high rates of recurrence and overall poor prognosis. Therefore, there is urgent need for novel targeted therapies for this aggressive AML subset. A multicenter, international team led by Richard Larson, MD, professor of medicine and director of the Hematologic Malignancies Program, tested whether the addition of an oral kinase inhibitor (midostaurin) to standard chemotherapy would improve outcomes for FLT3-mutated AML patients in a phase III clinical trial. Overall survival and event- free survival were significantly longer in the mido- staurin group, and the benefit of this new agent was consistent across all FLT3 subtypes (i.e., was not dependent on the precise type of mutation). Based on these clinical trial data, midostaurin was approved in April 2017 by the Food and Drug Administration (FDA) for adults receiving chemo- therapy for newly diagnosed AML with mutations in the FLT3 gene—the first new treatment for AML in almost two decades. (Stone et al., N Eng J Med 377:454-64, 2017) Trends for Allogeneic Hematopoietic Cell Transplantation in Older Adults In allogeneic blood (hematopoietic) stem cell transplantation, stem cells from a matching donor are collected and transplanted into a patient with blood cancer to suppress disease and restore the patient’s immune system. Although this therapeutic approach offers the best possible long-term dis- ease control, it wasn’t always thought to be suitable for older adults because of risk of toxicity and mortality. Recent advancements in the procedures and supportive care, however, have broadened its application to older adults. A research team involving the Center for Interna- tional Blood and Marrow Transplant Research and led by Andrew Artz, MD, associate professor of medicine, and former fellow Lori Muffly, MD (now at Stanford University), analyzed the incidence and outcomes of allogeneic stem cell transplantation performed in patients aged 70 or older. They found that there was increased utilization and survival after allogeneic transplant over the past decade. Specifically, the investigators reported a two-year post-transplant survival rate of 40 percent for patients in their 70s and 80s, providing evidence for the safety and feasibility of allogeneic stem cell transplantations for older adults. The data published in this study are particularly important because the incidence of almost all blood cancers increases with age and peaks in this patient population (>65 years) and they indicate that select patents aged 70 or older should be considered for transplantation. (Muffly et al., Blood 130:1156-64, 2017) Research Highlights (continued) Research 8 PATHWAYS TO DISCOVERY FALL 2017