BIDMC Researchers Help Define Risk in Multiple Myeloma Using Tumor Microenvironment Analysis
Large-Scale Study Maps Myeloma Tumor Microenvironment to Improve Risk Prediction
BOSTON — Scientists at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with the Multiple Myeloma Research Foundation (MMRF) and leading institutions across the country, have contributed to one of the largest efforts to date to map the cellular microenvironment of multiple myeloma tumors. The study, published in Nature Cancer, provides unprecedented insight into how immune cells surrounding the tumor can help predict which patients are at higher risk of disease progression.
Multiple myeloma is a blood cancer that, while treatable, remains incurable. Clinically, patients are often stratified into "high risk" or "low risk" groups based on genetic changes in the tumor that suggest how aggressively the disease may behave. However, current approaches to analyze these changes (known as cytogenetic analysis or scoring) do not fully capture why some patients relapse quickly while others respond well to therapy.
"Unfortunately, even the most advanced risk stratification methods still cannot accurately identify all patients who will face a more aggressive form of the disease," said Ioannis Vlachos, MD, PhD, an associate professor of pathology at BIDMC. "By capturing the immune microenvironment of the tumor — that is, the immune cells surrounding the tumor — we gain additional, highly valuable information not captured by any other available means. We showed that it can help us define patient risk, and especially when it is combined with the cytogenetic score, it could help us stratify patients more accurately and manage their treatment more effectively than is possible today."
BIDMC investigators teamed up with colleagues from Mount Sinai, Emory University, Washington University in St. Louis, and Mayo Clinic and analyzed nearly 1.5 million immune cells from the bone marrow of 335 newly diagnosed patients in the MMRF's CoMMpass study dataset using single-cell RNA sequencing. This detailed approach revealed patterns in the tumor microenvironment that are predictive of patient outcomes. Study co-author David E. Avigan, MD, Director of the Cancer Center at BIDMC, indicated that leveraging these sophisticated technologies to characterize how the immune system interacts with cancer cells in the tumor microenvironment will prove critical in understanding the spectrum of how cancer behaves and how best to design effective immune therapies.
Vlachos noted that the project underscores the importance of team science in tackling complex cancers.
"If you want to really capture the heterogeneity of a complex tumor such as multiple myeloma, which has proven to be a formidable foe, you need to work collaboratively and enable larger studies; bring together experts, technologies, and patient populations from across the nation. It is a complex task, but when everyone can maximally contribute for a common goal, it is extremely effective. It is magic.”
In addition, the research team has made this dataset publicly available, allowing other investigators to ask new questions about multiple myeloma biology and treatment.
"We do this work for the patients and it is enabled by the Multiple Myeloma Research Foundation, “Vlachos said. “We are certain that this powerful dataset and exciting discoveries will enable the multiple myeloma research community to move faster towards new biomarkers and therapeutics, benefiting our patients.”
Co-authors included Yered Pita-Juarez, Dimitra Karagkouni, Shivani Nanda, Yuling Ma, Giulia Cheloni, Isabella Saldarriaga, Jacalyn Rosenblatt of BIDMC; William C Pilcher of Georgia Institute of Technology; Lijun Yao, Yizhe Song, Kazuhito Sato, Julia T Wang, Reyka G Jayasinghe, Jennifer A Foltz, I-Ling Chiang, Li Ding, Mark A Fiala, Julie Fortier, Michael Slade, Stephen T Oh, Michael P Rettig, and Ravi Vij of Washington University in St. Louis; Zhihong Chen, Edgar Gonzalez-Kozlova, Darwin D'Souza, Rachel Chen, Kai Nie, Igor Figueiredo, Adeeb H Rahman, Junia Vieira Dos Santos, Alessandro Lagana, Sacha Gnjatic, and Seunghee Kim-Schulze of Icahn School of Medicine at Mount Sinai; Chaitanya R Acharya, Mark Hamilton, Jessica Schulman, Nick Pabustan, Eva Lepisto, April Cook, Hearn J Cho, and George Mulligan of MMRF; Marina E Michaud, Mojtaba Bakhtiari, Rania Alaaeldin, Beena E Thomas, Sagar Lonial, Swati S Bhasin, Sarthak Satpathy, Madhav V Dhodapkar, and Manoj Bhasin of Emory School of Medicine; Emilie Anderson, Ying Li, Surendra Dasari, Michael A Strausbauch, Vernadette A Simon, Shaji Kumar, and Taxiarchis Kourelis of Mayo Clinic.
This work was designed and funded by the Multiple Myeloma Research Foundation.
About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a leading academic medical center, where extraordinary care is supported by high-quality education and research. BIDMC is a teaching affiliate of Harvard Medical School, and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is the official hospital of the Boston Red Sox.
Beth Israel Deaconess Medical Center is a part of Beth Israel Lahey Health, a healthcare system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,700 physicians and 39,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.
