This grant award will facilitate a multidisciplinary research project that will analyze a large, diverse cohort of patient samples from all over the United States at the genomic and immune level and apply novel functional genomics technology to understand the critical events that drive high-risk multiple myeloma and lead to treatment resistance. The project will also use state-of-the-art CRISPR genomics, spatial imaging, and chimeric antigen receptor (CAR) T cell technology to identify new therapeutic targets and drug modalities that can be harnessed for more effective treatments for high-risk multiple myeloma.
Multiple myeloma is a blood cancer that develops in the bone marrow and can spread throughout the body. In 2023, more than 35,000 Americans are projected to be diagnosed with multiple myeloma and approximately 12,000 will lose their lives. Despite advances, most patients relapse and there is still no cure. Multiple myeloma is twice as common in the Black community as in other ethnicities, and genetics and immune changes contributing to high-risk disease have not been elucidated.
“Advances in immunotherapy and novel agents have improved long-term outcomes for most myeloma patients, but a subset with high-risk newly diagnosed myeloma have early disease progression and inferior outcomes,” said Principal Investigator Samir Parekh, MD, Director of Translational Research in Multiple Myeloma and co-leader of the Cancer Clinical Investigation program at The Tisch Cancer Institute, a part of the Tisch Cancer Center at Mount Sinai. “We lack a detailed understanding of the genomic and immunologic differences between high-risk and standard-risk patients, and current trials with novel T cell therapeutics in relapsed myeloma continue to show shorter survival in high-risk patients. All of this highlights the urgent need for greater research efforts and new treatments for these vulnerable patients.”
This project is jointly led by Dr. Parekh and Brian Brown, PhD, Director of the Icahn Genomics Institute and Associate Director of the Marc and Jennifer Lipschultz Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. Dr. Brown said, “Through this endeavor, we expect to identify the genes responsible for high-risk myeloma growth and resistance to immunotherapy, as well as to identify novel targets for cellular therapy and bispecific antibodies.”
“Ultimately, our research network stands to greatly improve our comprehensive understanding of high risk myeloma and rapidly translate this knowledge into next-generation clinical trials for patients who desperately need novel therapeutic strategies,” said Sundar Jagannath, MD, Mount Sinai Professor in Multiple Myeloma and Director of the Multiple Myeloma Center of Excellence at the Tisch Cancer Center.
Mount Sinai is leading a network of researchers from institutions that include Albert Einstein Medical College, Hackensack University Medical Center, Stanford University Medical Center, University of California San Francisco, and Washington University in St. Louis.
Researchers hope to uncover the full landscape of genomic, proteomic and immune differences between high- and standard-risk multiple myeloma patients. They also hope to identify which differences drive faster myeloma progression and resistance to therapy and understand precisely how these differences influence treatment responses.
Mount Sinai was one of three teams to receive the highly competitive grant from MMRF as part of its Myeloma Accelerator Challenge (MAC) Program Grants. Each of these prestigious three-year multicenter translational projects is designed to advance compelling hypotheses that are ready for rapid testing in clinical trials, a critical step in the MMRF’s urgent pursuit of a cure for every myeloma patient.
“Our MAC Grants enable us to fund research that is highly focused and, by requiring multiple centers to work in a network, also highly collaborative,” said George Mulligan, PhD, Chief Scientific Officer at the MMRF. “The three exciting programs we selected each have potential to answer fundamental questions about multiple myeloma and help advance rational treatments for this cancer.”
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report‘s Best Hospitals, receiving high “Honor Roll” status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children’s Hospital among the country’s best in several pediatric specialties.