Our clinical research efforts over more than 20 years have contributed to the development of most of the current WM treatments. Many of the treatments came from laboratory discoveries, including translational efforts that identified Bruton’s Tyrosine Kinase as a key molecule that promotes survival of WM cells by mutated MYD88. This practice-changing discovery resulted from our discovery of MYD88 as the most prevalent mutation in WM through whole genome studies. These findings led to the approval and use of BTK-inhibitors for the WM treatment.
Our Center offers patients access to many clinical research trials. The main goal of our clinical research is to quickly and efficiently take discoveries made in the laboratory to the clinic, where they can benefit the health and well-being of patients.
22-611: A phase 2 study to evaluate the safety and efficacy of venetoclax combined with pirtobrutinib in participants with symptomatic Waldenström's Macroglobulinemia (WM) with previously treated disease
Principal Investigator: Jorge Castillo, MD
21-622: A phase 2 study to evaluate the safety and efficacy of loncastuximab tesirine in patients with Waldenström Macroglobulinemia (WM) who have received at least 2 prior treatments, including an anti-CD20 antibody such as rituximab and a BTK inhibitor such as ibrutinib
Principal Investigator: Shayna Sarosiek, MD
The Bing Center has attracted some of the most accomplished scientists to develop new, biologically based treatments for WM. The Center is led by Steven Treon, MD, PhD, and is funded through competitive grants supported by the National Institutes of Health, The Leukemia and Lymphoma Society, the International Waldenström’s Macroglobulinemia Foundation, the Waldenström’s Macroglobulinemia Foundation of Canada, and numerous private philanthropies and benefactors.
Zachary Hunter, PhD, is a principal scientist and Associate Director for the Bing Center Laboratory. Dr. Hunter is the incumbent of the Tim and Ginny Bliss Investigator Chair for the Genomic Study of WM, and a recipient of the prestigious Robert A. Kyle Award for Outstanding Contributions to WM for his pioneering work in the discovery of MYD88 and CXCR4 mutations in WM. Dr. Hunter is working with his laboratory team to study the multi-omics of 300 WM patients (300 project) representing one of the largest efforts to study the combined genome, transcriptome, and epigenome in any lymphoma. Their efforts, recently reported in an oral presentation at the 64th Annual Meeting of the American Society of Hematology, identified 4 distinct clusters of WM patients, each with different genomic characteristics and potential treatment outcomes, paving for a more personalized approach to WM care.
Kris Richardson, PhD, is a senior scientist in the Bing Center for WM who was trained at the Broad Institute and is exploiting the multi-omic findings of the 300 project to understand fundamental differences between WM patients, including those that have a familial predisposition. Our better understanding of such differences may help in efforts to personalize treatment approaches, including efforts to prevent progression of WM disease. Dr. Richardson is also using high resolution mapping to clarify what genomic regions may be responsible for WM predisposition.
Shirong Liu, MD, PhD, who is the incumbent of the Lee and Michael Bell Fellowship for Translational Medicine at the Bing Center for WM, is exploiting genomic findings to advance novel drugs for WM. His efforts have identified vulnerabilities in the circuitry that allows mutated MYD88 to stimulate WM cell growth and survival. He is also leading an effort to understand how WM cells can “neutralize” immune cells from responding and killing malignant cells through single cell RNA analysis of the bone marrows of WM patients.
Xia Liu, MD, is a senior scientist at the Bing Center for WM and is responsible for leading transduction experiments that help characterize how mutated genes work in WM cells. Her efforts helped identify the critical role of HCK and BTK in the signaling of mutated MYD88, and the importance of BTK Cys481 mutations in the development of ibrutinib resistance. The latter helped inform the critical nature of ERK signaling in the development of ibrutinib resistance and the advancement of ERK suppressing therapies.
John Hatcher, PhD, who is a principal scientist in the Bing Center, is a medicinal chemist with extensive expertise in drug development. He has developed highly potent and selective inhibitors that target key components of mutated MYD88 signaling including HCK and IRAK inhibitors that have shown very promising results in early pre-clinical testing.
Maria Luisa Guerrera, MD, is a hematologist, an Instructor of Medicine at Harvard Medical School, and a recipient of the Robert A. Kyle Career Development Award from the International Waldenström’s Macroglobulinemia Foundation. Dr. Guerrera is studying the genomic events that are responsible for WM disease progression following acquisition of the MYD88 mutation. Her work, which was recently reported in an oral presentation at the 64th Annual Meeting of the American Society of Hematology, identified the WNK2 gene as a major enabler of WM disease formation by impacting the ERK signaling network.