The Bing Center for Waldenström’s Macroglobulinemia At the Forefront of Discovering and Delivering Treatments for Waldenström’s Macroglobulinemia

Dana-Farber Cancer Institute’s Bing Center for Waldenström’s Macroglobulinemia is a leading global research and patient care center. For almost two decades, the Bing Center has provided specialized treatment to patients diagnosed with Waldenström’s macroglobulinemia (WM). It is the only center in the world dedicated to patients with WM and discovering the genetic origins of the disease.

About Waldenström’s Macroglobulinemia

Waldenström’s macroglobulinemia is a rare slow-growing cancer that was first described by Swedish physician Jan G. Waldenström in 1944. The disease is characterized by the growth of abnormal B-lymphocytes in the bone marrow and in some patients, spreading to the lymph nodes, spleen, and brain.

Approximately 1,500 patients are diagnosed with WM per year in the United States.

While treatment options for WM have expanded in recent years, thanks in great part to basic science and clinical research fulfilled at the Bing Center, there is still a need for more durable cures.

The First to Define the Unknown

Steven Treon, MD, PhD, director of Dana-Farber’s Bing Center, and his colleagues spearheaded the world’s first whole-genome sequencing project for WM, which led to the identification of MYD88 – a genetic mutation that underlies more than 95% of WM cases, and CXCR4, which is found in 40% of WM patients. These discoveries have helped advance diagnostic, prognostic, and treatment advances for WM. The Bing Center team also developed a diagnostic test for the MYD88 mutation, which helps to diagnose WM earlier and distinguish WM from other diseases.

More than 95% of WM patients carry a mutation in the MYD88 gene.

40% also have a mutation in the CXCR4 gene.

Expertise in Action: Steven Treon, MD, PhD

Treon has specialized in WM at Dana-Farber for over 25 years, cementing his legacy of life-saving contributions to WM research and care. In 1999, Treon founded the WM program, later named the Bing Center, in response to his nagging frustration and curiosity about the disease – and his confidence that he could make a difference. With the help of patients, caregivers, and Institute scientists, Treon’s leadership has enabled Dana-Farber to advance our understanding of the causes of WM and to accelerate the development of novel therapies. His relentless pursuit supported Food and Drug Administration (FDA) and European Medicine Agency (EMA) approvals of breakthrough WM treatments, which permanently altered the landscape of WM care. The Bing Center team is now 20 strong, and while outcomes for WM have drastically improved, Treon and his colleagues continue to strive to develop more effective, less toxic treatments, and a cure.

20 years of Breakthrough Discoveries

The groundbreaking discoveries made at the Bing Center have revolutionized the treatment of WM at Dana-Farber and around the world.

Treon and colleagues identify rituximab as a highly active drug to treat WM; rituximab becomes a foundational therapy for Waldenström’s macroglobulinemia.

Waldenström’s macroglobulinemia is officially named a clinicopathological entity, as defined by the World Health Organization (WHO) and Revised European & American Lymphoma (REAL) classification systems.

The WM program at Dana-Farber is officially renamed as the Bing Center for Waldenström’s Macroglobulinemia in honor of Peter S. Bing, MD, nationally renowned philanthropist and public health expert.

The Bing Center defines the incidence and characteristics of the familial form of WM based on disease cluster patterns, advancing research into studies to detect genetic predispositions.

Treon and his colleagues report on the establishment of BCWM.1, a WM representative cell line that acts as a model for researchers to study and test targeted therapies against.

The International Prognostic Scoring System for Waldenström’s Macroglobulinemia (IPSSWM) is established to optimize treatment, compare global clinical trials, and estimate long-term outlooks for patients.

Bortezomib, a proteasome inhibitor, is introduced for single and combination therapies in WM.

Treon is the first to identify that MYD88 mutations as the most prevalent mutation in WM, with over 95% of patients carrying this mutation. The discovery is reported in The New England Journal of Medicine.

Mutations in CXCR4 are determined to occur in about 40% of WM patients. The Bing Center team reports that CXCR4 mutations impact drug therapy, including BTK-inhibitors.

The FDA approves the breakthrough therapy ibrutinib, a BTK inhibitor that suppresses MYD88 survival signaling. Ibrutinib becomes the first drug ever approved for WM. Treon is the lead investigator for this study.

The FDA approves a second treatment, a combination therapy of ibrutinib plus rituximab, resulting in significantly higher rates of progression-free survival for patients with WM.

The 300 Project is launched, a tissue banking and sequencing effort to map the genetic alterations (DNA, RNA, and epigenome) from 300 patients with untreated WM under the direction of Treon and Zachary Hunter, PhD.

The FDA approves a next-generation BTK inhibitor, zanubrutinib, for WM treatment. Zanubrutinib shows better tolerance versus ibrutinib by most patients.

Treon’s team identifies two powerful targets (IRAK1/IRAK4, HCK) that are critical to MYD88 signaling and response to BTK-inhibitors. John Hatcher, PhD, is recruited to be the chief medicinal chemist for the Bing Center and develop targeted degraders that eliminates these proteins.

Venetoclax demonstrates a high response rate in a multicenter clinical trial, proving effective even in patients previously exposed to BTK inhibitors or refractory to prior treatments. The National Comprehensive Cancer Network (NCCN) endorsed it for patients with previously treated WM. Bing Center Clinical Director Jorge Castillo, MD was the study's principal investigator.

Under Castillo’s leadership, the Bing Center established the Waldenström’s Macroglobulinemia Network (WM-NET), a think tank composed of more than 20 academic institutions in the U.S. interested in developing prospective clinical trials in WM.

Bing Center Senior Physician Shayna Sarosiek, MD is leading current and soon-to-open immunotherapy focused clinical trials investigating loncastuximab and CAR T-cells.

Research Saves Lives

In 20 years, the Bing Center has fundamentally improved the outcomes for WM patients. Treon and his colleagues have defined the genetic blueprint of WM with the novel findings of MYD88 and CXCR4 and brought forth game-changing FDA-approved treatments for WM. Investigators continue studying therapies even after FDA approval so they can gather new insights to improve the use of those therapies and to optimally select the patients for whom they are effective. Together these discoveries have improved overall survival from three to five years to decades.

The Medicinal Chemistry Core: Dana-Farber’s Competitive Edge

Dana-Farber's Medicinal Chemistry Core is a specialized facility dedicated to advancing drug discovery by collaborating with researchers in the design, synthesis, and optimization of small molecules for use as chemical tools and therapeutic agents. The core supports both academic and industry partners, offering expertise in managing synthetic chemistry projects. The development of new pharmacologic agents requires extensive chemical explorations which makes the Medicinal Chemistry Core an invaluable asset to the Bing Center, as it screens thousands of combinations of chemical compounds against WM targets.

Read more about the Medicinal Chemistry Core here.

Philanthropy fuels progress

Due to the rarity of WM, research on WM is underfunded by traditional sources, including government agencies and the pharmaceutical industry. Philanthropy plays a crucial role in filling this gap by providing physician-scientists with flexible resources to test innovative approaches to research and drug discovery. Funding from philanthropy is essential to early stage pilot studies, which can result in findings that attract financial investments from other sources, including National Institute of Health (NIH) grants and the pharmaceutical industry.

The above are estimates of annual funding sources for the Bing Center.

With philanthropic support, we can help more patients live longer, healthier lives.

Eric and Harriet Kaplan

When Eric Kaplan was first diagnosed with WM, his local hematologist was forthright about the rarity of the disease and that he had seen fewer than twenty cases in his entire career. He was supportive of Kaplan seeking a second opinion at Dana-Farber, and it was at the Bing Center that Kaplan received the treatment that changed his life. “Because of my participation in a clinical trial, I am hopeful that I will see my two-year-old grandson, Eli, graduate high school,” said Kaplan. “Just a year ago, seeing Eli graduate kindergarten was only as far out as I felt comfortable discussing.” Kaplan and his wife, Harriet, want other WM patients to enjoy the family milestones they themselves have reached because of the treatment he received at Dana-Farber.

“What’s very exciting to me is that the WM Network will allow so many more WM patients to participate in clinical trials than have been able to historically.”

The Kaplans have become avid supporters of the Bing Center. They understand the power of philanthropy and are working to galvanize support from other members of the WM community, including other patients and their loved ones. In 2023, the Kaplans helped to launch the WMNET, a coalition of over 20 academic institutions collaborating to develop potential clinical trials in WM, which is sustained solely by philanthropy. “The WM Network has the potential to greatly accelerate the understanding of WM and the care of WM patients,” Kaplan remarked. “What’s very exciting to me is that the WM Network will allow so many more WM patients to participate in clinical trials than have been able to historically.”

Your Opportunity for Impact

Philanthropic support for the following priorities will enable the Bing Center to expedite research, cultivate generations of WM experts, and transform the lives of WM patients and their families.

Revolutionary Science

Dana-Farber is committed to supporting discovery science to bring the next generation of lifesaving treatments to patients. Philanthropy enables the team of experts in the Bing Center to:

Pursue foundational basic research that helps researchers understand the body’s cellular and molecular mechanisms that drive WM to proliferate.

Expedite translational research that brings basic science discoveries from the lab into new cancer medicines in the clinic.

Lead clinical trials of promising therapies and novel combinations of drugs to bring new treatment options to WM patients who have developed resistance to treatment or have a subtype of WM that does not respond to first-line therapies.

Technology & Resources

The Bing Center’s state-of-the-art research infrastructure provides the foundation for innovative discoveries by:

Enhancing diagnostics that are more accessible and can perform less invasively.

Reimagining WM drug development using chemo-proteomics to identify potential compounds that bind to cancer-causing proteins and degrades them to yield more effective treatment options.

Deploying single cell sequencing to understand how cells communicate with each other to promote WM.

Screening hundreds of drug compounds to generate proof-of-concept data by leveraging Dana-Farber’s Medicinal Chemistry Core.

Resource Spotlight: The 300 Project

The 300 Project is the largest genetic, transcriptional, and regulatory dataset supporting the mapping of genetic alterations found in 300 patients with untreated WM and is funded almost exclusively by philanthropy. The project aims to identify disease subtypes that suggest which drugs might be successful in a particular group of patients. Researchers with the NIH’s International Lymphoma Epidemiology Consortium have leveraged 1,000 patient samples from the Bing Center to identify several new predisposition markers in the genome.

Exceptional Expertise

Dana-Farber provides the highest quality training to faculty and staff responsible for advancing discoveries and delivering exceptional patient care. Donor support guarantees that Dana-Farber continues to attract, retain, and recognize the most talented individuals in the fiercely competitive field of biomedical research.

Funding Opportunities

The Bing Center Research Fund – Make a gift online to support the Bing Center research mission: Bing Center Giving Page

Named Current-Use Funds ($100,000) Current-use funding can be earmarked for specific research and care opportunities under the leadership of a Bing Center investigator. Commitments at this level are recognized with several benefits, including the opportunity to name your fund in honor of your family or loved one.

Named Endowed Funds ($500,000) – Gifts to establish endowed funds provide ongoing support to ensure Dana-Farber remains at the forefront of innovative research and patient care by attracting, retaining, and rewarding the best and brightest physician-scientists in the field. An endowed fund can also represent a legacy for your family that will endure in perpetuity for generations.

Named Term Fellowships ($500,000) A gift to name a fellowship provides two years of financial support to the fellowship recipient, who is an investigator in the Center. With this support, you can meet with the incumbent annually and hear about the impact of your gift on their career development.

Endowed Chair ($3,000,000)

Endowed Chairs at Dana-Farber are powerful tools to retain, attract, and support exceptional talent. One of the highest accolades to recognize senior faculty, a Dana-Farber Chair honors and recognizes a distinguished faculty member and provides invaluable financial support in perpetuity to pursue essential research priorities. The incumbent is a professor or associate professor at Harvard Medical School. Learn more about endowed Chairs here.

Investigatorship ($2,000,000)

An endowed Investigatorship provides funding for an exceptionally creative and committed faculty member at a vital point in their career. It helps the Institute attract and retain faculty of the highest quality, and it ensures that important research directed by the Investigator is continuously funded. An Investigatorship provides annual income in perpetuity to an outstanding scientist or clinical researcher for basic and translational research and the best in patient care. The incumbent is an assistant or associate professor at Harvard Medical School.

Philanthropy Spotlight: Tim & Ginny Bliss

Tim Bliss, of Santa Barbara, California, is one of the 1,500 patients each year diagnosed with WM. That’s why Tim and his wife, Ginny, gave Dana-Farber $2.2 million to establish an investigatorship to support the work of Zachary Hunter, MD, a mid-career computational biologist, to be named the inaugural incumbent. By endowing the new investigatorship, said Tim Bliss, “we feel we’re supporting research for a disease that doesn’t get a lot of financial support, and a team that’s really exceptional, passionate, and capable.”

Tim & Ginny Bliss

Fellowship ($1,000,000)

Dana-Farber honors its responsibility to shape the next generation of leaders in cancer research and patient care by prioritizing vital training pathways for physicians early in their career. Help prepare a new generation of academically oriented physicians to become leaders in clinical and laboratory investigation, clinical care, and education. Investment in our Waldenström’s faculty and programs has the power to prepare a new generation of promising physicians to become tomorrow’s leaders in the clinic and lab.

Thank you for your interest in supporting Dana-Farber’s mission to defy cancer.

To learn more, please contact:

Jenn Musso, Senior Director, Principal & Major Gifts | JenniferN_Musso@dfci.harvard.edu | 617-632-6550

Andrea Hadfield, Managing Director, Foundation Relations | Andrea_Hadfield@dfci.harvard.edu | 617-632-4906