Physician-scientist Dr. David Maloney is at the forefront of clinical trials to develop cell therapies for blood and other cancers, including understanding side effects of CAR T’s and how to deliver them in outpatient settings. A renowned researcher and clinician focusing on cancer immunotherapies and CAR T-cell therapies, he recently presented findings from the TRANSCEND trial for CD19 CAR T. This study showed that patients had improved quality-of-life (reduced fatigue and pain symptoms) starting six months after receiving CAR T-cell therapy. Dr. Maloney focuses on using genetically engineered T cells (such as CAR-T) to treat patients with leukemia, lymphoma, myeloma and selected other cancers without causing graft vs. host disease that has been associated with transplantation. He was instrumental in developing and testing rituximab, the first antibody-based cancer drug on the market – one that has transformed the treatment of certain leukemias and lymphomas. He is also an expert on blood-forming (hematopoietic) stem cell transplantation (HCT) in using a matched donor’s (allogeneic) or a patient’s own (autologous) stem cells in treatments for patients with hematologic malignancies. Recognizing that standard pre-transplant regimens are too toxic for many patients, Dr. Maloney and Fred Hutch colleagues are evaluating approaches that use antibodies to deliver radioactivity or cancer-killing drugs directly to tumors. They have also developed a less toxic, “reduced intensity” (nonmyeloablative) regimen that can more safely provide long-term remissions for patients with chronic lymphocytic leukemia (CLL), non-Hodgkin Lymphoma (NHL) and myeloma after allogeneic HCT. Autologous HCT followed by reduced intensity allogenic HCT (tandem HCT) has proven effective for refractory NHL and myeloma patients. Dr. Maloney and colleagues have learned that nearly all of the anti-tumor activity of allogeneic HCT comes from the specific graft-vs-tumor activities of donor immune T cells, showing that antitumor immunity can be curative. Unfortunately, these T cells can also cause dangerous “graft-vs-host” effects on normal tissues. Dr. Maloney continues exploring the use of antibodies as anti-cancer therapies, including newer anti-CD20 antibodies (e.g. ofatumumab, Arzerra®) for NHL patients, as well as radiolabeled antibodies, drug-carrying antibodies and unlabeled antibodies as targeted pre-transplant “conditioning” or as “maintenance” to extend remissions after allogeneic transplantation. As medical director of the Cellular Immunotherapy Integrated Research Center at Fred Hutch, Dr. Maloney cares for patients at the Bezos Family Immunotherapy Clinic at Seattle Cancer Care Alliance, the Hutch’s clinical-care partner. He is also professor of medicine in the Division of Oncology at the University of Washington.
“The current CAR T-cell therapies need to become more effective, more affordable and safer. We need to understand why they do not work for certain people, why they only work in select types of cancer and why they can cause severe, occasionally fatal, side effects.”
“It shows the unbelievable power of your immune system."