Therapeutic Trials
For Low-Risk Plasma Cell Disorders
Reform is for patients with high-risk MGUS and low-risk SMM and evaluates the role of metformin in precursor plasma cell disorders. This randomized, placebo control trial aims for stabilization of disease markers to help reduce risk of progression to multiple myeloma.
For High-Risk Plasma Cell Disorders
Immuno-PRISM is a phase 2 randomized platform study evaluating the effectiveness of various novel immunotherapy-based treatments in preventing disease progression in patients with high-risk SMM. At this time, the highly effective bispecific antibody targeting BCMA, teclistamab, is being compared to the standard therapy of lenalidomide and dexamethasone. Future treatment arms will be added to the study as they become available.
B-PRISM is a phase 2 study that utilizes a highly effective combination strategy of daratumumab, bortezomib, lenalidomide, and dexamethasone in high-risk SMM. Our goal is to achieve high rates of minimal residual disease (MRD) negativity in patients with high-risk SMM.
CAR-PRISM is the first study of the highly effective BCMA directed CAR T-cell therapy, ciltacabtagene autoleucel (cilta-cel), in patients with high-risk SMM. This is a single-arm, non-randomized trial to study the benefit and safety of administering CAR T-cell therapy at an early stage of the disease to prevent development of multiple myeloma.
Non-Therapeutic Trials
PCROWD is an ongoing research study that collects tissue samples from patients with precursor hematologic conditions. Our goal is to understand the cellular changes associated with disease progression so that we can develop targeted therapies to prevent progression to cancer. The study has helped identify mutations associated with disease progression. Patients with any precursor blood cancer condition are eligible to participate in the PCROWD study.
IMPACT aims to identify the presence and development of COVID-19 in individuals with precursor hematologic conditions compared to healthy populations in order to understand the short- and long-term impact of COVID-19 on the immune system. Participants will be screened for SARS-CoV-2 seropositivity and will then be followed and undergo additional blood collection and testing for one year.
PROFAST is a 4-month randomized trial of a prolonged nightly fasting intervention (PROFAST) in 40 overweight and obese individuals with MGUS, SMM, and smoldering Waldenström macroglobulinemia (SWM). The purpose of this study is to understand if fasting for a prolonged period of time during the nighttime hours is a strategy to improve metabolic health and prevent overweight and obese individuals from developing blood cancer.
Research Highlights
Our team was the first to discover CHIP and its link to blood cancers and cardiovascular disease, and has been leading several efforts to understand the genomic, genetic, and epigenetic factors that influence disease progression for other precursor conditions. We offer several clinical trials of early therapeutic intervention to prevent progression and cure the disease in its early state.
Clonal Hematopoiesis of Indeterminate Potential (CHIP)
Benjamin Ebert, MD, PhD, made the landmark discovery identifying clonal hematopoiesis of indeterminate potential (CHIP), a precursor condition that is detectable in over 10 percent of people over age 70, and was the first to describe the increased risk of blood cancers and cardiovascular disease in people with CHIP.
Age-related clonal hematopoiesis linked to adverse outcomes, New England Journal of Medicine, 2014 November 26
Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes, Blood, 2015
MGUS, MGIP
Irene Ghobrial, MD, led the first effort to screen individuals at high risk of developing myeloma, including those with family members who have multiple myeloma or self-identify as Black, for the precursor conditions MGUS and smoldering myeloma. This team defined a new clinical entity, MGIP, defined by the presence of a low level of M-protein. All screen-detected monoclonal gammopathies were associated with increased mortality and increased prevalence of comorbidities including myocardial infarction, certain blood cancers, and some autoimmune disorders.
Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study, The Lancet Haematology, 01 May 2022
Smoldering Multiple Myeloma
Nikhil Munshi, MD, and his colleagues have identified the genomic changes that occur as smoldering multiple myeloma (SMM) advances to myeloma. Their findings lay the groundwork for tests that can identify patients whose SMM is likely to progress rapidly to myeloma, and who could benefit from prompt treatment.
Irene Ghobrial, MD, Mark Bustoros, MD, and others have led research of the molecular characterization of precursor malignant cells to improve our understanding of the biological development of myeloma, as well as risk stratification and prognosis for patients.
Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes, Nature Communications, 15 June 2022
A paper by Yoshinobu Konishi and Irene Ghobrial, MD, explores the impact of SMM on the immune system by analyzing patients' antibody responses to COVID-19 infection and vaccination. The team found that SMM patients had less robust responses to vaccination than healthy individuals, which aligns with findings in myeloma patients.
Attenuated response to SARS-CoV-2 vaccine in patients with asymptomatic precursor stages of multiple myeloma and Waldenstrom macroglobulinemia, Cancer Cell, 10 December 2021
