BS (Chemistry): Whitworth College; Spokane, WA; 1977
MD (Medicine): Stanford University; Stanford, CA; 1985
Internal Medicine Fellowship: Brigham and Woman's Hospital; Boston, MA; 1985-1988
Medical Oncology Fellowship: Stanford University; 1988-1994
PhD (Cancer Biology): Stanford University; 1991
Dr. Maloney is widely recognized as an expert in the treatment of lymphoma, myeloma and CLL, including antibody-based treatments, reduced-intensity allogeneic HCT for NHL, CLL and myeloma patients and autologous HCT for lymphoma and myeloma patients. He is currently leading a clinical trial that is evaluating T cells that carry a synthetic, tumor-seeking molecule (a chimeric antigen receptor) for patients with CD19 positive malignancies including acute lymphoblastic leukemia (ALL), CLL and NHL. The use of CAR- T cells represents an exciting approach to engineer tumor immunity.
Dr. Maloney’s research is focused on the development of new, safe and effective therapies for patients with lymphoid cancers, including lymphomas, leukemias and myeloma. His primary focus is treatments that can enhance anti-cancer immune responses, collectively known as immunotherapies. One strategy uses immune cell products known as antibodies. Dr. Maloney led the initial development of the anti-CD20 antibody Rituximab (Rituxan®), and continues to study therapeutic monoclonal antibodies in the laboratory and in the clinic.
At the Fred Hutch, his primary clinical focus is blood-forming (hematopoietic) stem cell transplantation (HCT). He is an expert 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. Therefore, they are now carefully studying genetically engineered T cells that can more selectively target cancers, in the lab and in clinical trials.
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.
In the ongoing CAR-T clinical trial, potent anti-tumor activity has been observed in patients with leukemia and lymphoma, but some lymphoma patients have had only partial remissions. Therefore, in addition to continuing to develop new antibody-based therapies in laboratory models, Dr. Maloney is working to understand the interactions between the CAR-T cells and the tumor microenvironment, including the potentially inhibitory effects of other types of immune cells and of the tumor cells themselves. Findings should provide opportunities to further improve CAR-T cell therapy and make it a lifesaving option for more patients.
Studies on which Dr. Maloney plays a leadership role and are currently enrolling participants include:
Dr. Maloney is also planning a clinical trial that will test two of the newest targeted drugs as post-transplant “maintenance” therapy for patients with persistent or relapsed B-cell malignancies. He and Fred Hutch colleagues are developing new immunotherapy trials as well.