The Waldenstrom’s Macroglobulinemia program at Dana Farber Cancer Institute (DFCI) was founded in 1999 by Dr. Steve Treon with the help of patients, caregivers and DFCI scientists in an effort to advance our understanding of the cause of WM, and to pursue novel therapies. In 2005, the WM program was officially designated as the Bing Center for WM, in honor of Peter S. Bing M.D., former Chair and current Trustee of Stanford University. The Bing Center for WM attracts hundreds of patients each year from all over the world, and is the largest referral center for this disease. The WM clinic is involved in numerous intra- and extramural collaborative studies into the natural history, morbidity, genetic predisposition, and treatment of WM, and has served to extend training in this uncommon disease to medical students, residents, physicians, and allied health care givers. Each year, several internationally recognized WM experts are invited to participate as visiting professors.
Among the accomplishments of the Bing Center for WM has been in defining the incidence and clinicopathological characteristics of the familial form of WM which effects about 20% of all WM patients, and is characterized by the presence of WM or other B-cell malignancies among relatives of WM patients. To further efforts into the familial form of WM, the Bing Center for WM established a family registry which is supported by a major grant from the International WM Foundation. The family registry has recruited over 600 WM patients and their family members. These studies have led to important insights into the genetic basis of WM including the identification of increased incidence of hypogammaglobulinemia and monoclonal gammopathy in family members of patients with WM, as well as the identification of mutations in genes predisposing to Common Variable Immunodeficiency Disorder (CVID) in WM patients. In order to determine the genetic basis of WM, ongoing studies at the Bing Center for WM have been utilizing array cGH, microRNA and gene expression profiling studies of tumor and micro-environmental cells in WM, which have led to the identification of signaling pathways supportive of the growth and survival of WM cells. These efforts have also led to the identification of bone marrow mast cells (BMMC) as potent inducers of tumor cell growth in WM patients through interactions involving CD154-CD40, a pathway induced by tumor cell secretion of soluble CD27. These revelations have helped establish the importance of targeting mast cells and their tumor cell interactions in the treatment of WM, and have resulted in several clinical trials exploiting these findings. In addition, the Bing center for WM has also focused on the development of novel therapeutics by exploiting gains made in our basic science understanding of WM, as well as predictive testing for the efficacy of such agents such as the use of polymorphisms in the CD16 receptor to predict responses to rituximab.
An important complement to the basic research efforts into WM has been the conduct of clinical trials solely dedicated to WM patients. As part of these efforts, the Bing Center for WM organized the Waldenstrom’s Macroglobulinemia Clinical Trials Group (WMCTG) which has conducted multi-center clinical trials utilizing monoclonal antibodies alone and in combination with nucleoside analogs, cytotoxic and immunomodulating agents, and the proteasome inhibitor bortezomib, as well as single agent studies with phosphodiesterase, stem cell factor and mTOR inhibitors. These studies helped establish the role of rituximab (Rituxan®), alemtuzumab (Campath-1H®), bortezomib (Velcade®), and thalidomide (Thalomid®) in the treatment of WM. Clinical studies from the Bing Center for WM have also led to the recognition of important short and long term consequences of WM related treatments including: 1) identification of the rituximab induced IgM flare; 2) lenalidomide-related aggravated anemia; 3) increased risk of bortezomib-related neuropathy, and development of shingles (herpes zoster) with use of bortezomib/steroid combinations; and 4) long term risk of secondary malignancies with nucleoside analogues (fludarabine, cladribine). The findings of these studies have been published in major peer reviewed journals and have lead to changes in the published consensus approaches to the treatment of WM patients.
Lastly, an important focus of the Bing Center for WM has been physician and patient education. Among the accomplishments of the Bing Center for WM has been the organization of the 2nd (Athens, Greece), 3rd (Paris, France), 5th (Stockholm, Sweden), 6th (Venice, Italy) and 7th (Newport, RI, USA) International Workshops for WM, the International Symposiums on WM held as part of the International Myeloma Workshops (Banff, Canada; Salamanca, Spain; Sydney, Australia; Kos, Greece), and the International Conference on Malignant Lymphoma (Lugano, Switzerland), the 1st (Boston, USA), 2nd (Los Angeles, USA), 3rd (Boston, USA) and 4th (Orlando, USA) International Patient/Physician Summits on WM, as well as local and regional WM support group meetings in the U.S., Canada, Europe, and Australia.