Research Projects

The MMRF CoMMpass study is a groundbreaking longitudinal and observational clinical research initiative designed to comprehensively map the biology, progression, and treatment outcomes of multiple myeloma. Launched in 2011 and completed in 2023, the study enrolled 1,143 patients with newly diagnosed active multiple myeloma and followed them over eight years to capture the full trajectory of the disease.

Through serial bone marrow and peripheral blood sampling at critical clinical milestones—including baseline, remission, progression, and relapse—CoMMpass generated one of the most complete molecular portraits of any cancer cohort to date. The initiative integrated whole-genome sequencing, whole-exome sequencing, and transcriptome profiling with rich, longitudinal clinical data. The study has provided unparalleled insights into disease progression, treatment responses, and survival.

The depth and quality of the CoMMpass dataset has established it as a foundational resource for precision medicine in multiple myeloma. Its discoveries continue to shape disease classification, inform treatment strategies, and power translational research across academia and industry—advancing the field towards improved patient outcomes.

Selected publications:

• Skerget et al., Nature Genetics 2024
  
• D'Agostino et al., Clin. Cancer Res. 2020
  

Conducted as part of the MMRF CoMMpass Study, this program provides unprecedented insight into the immune architecture of multiple myeloma. By profiling over 1.39 million single cells from the bone marrow of 335 newly diagnosed patients, the study delivers a high-resolution view of immune and hematopoietic cell populations that influence disease biology.

Through integrated single-cell transcriptomics and genomic characterization, the study identifies immune ecosystems and cellular states associated with disease progression, therapeutic response, and relapse risk. By linking immune cell composition and phenotypes with underlying genetic features, the program enhances patient stratification and reveals biomarkers and pathways that may guide the development of next-generation immunotherapy strategies.

This work represents one of the most comprehensive characterizations of the myeloma immune microenvironment to date and serves as a foundational resource for mechanistic discovery and precision immune-oncology research.

Selected publications:

• Pilcher et al., accepted in Nature Cancer
  

The MyDRUG study—also known as Myeloma Developing Regimens Using Genomics—is a pioneering precision-medicine platform trial designed to evaluate personalized treatment regimens for multiple myeloma patients based on their tumor’s genomic profile. Conducted across 16 clinical centers in the United States (ClinicalTrials.gov identifier NCT03732703), the study analyzes bone marrow tumor samples to identify actionable genetic mutations and match patients to targeted therapies tailored to their molecular subtype.

The trial aims to:

• Identify and validate genomic alterations in multiple myeloma that can be therapeutically targeted
• Develop and test individualized treatment regimens informed by patients’ genomic profiles
• Improve clinical outcomes and quality of life through precision-medicine approaches

By linking genomic insights with therapeutic selection, MyDRUG represents an ambitious effort to operationalize precision medicine in multiple myeloma, offering a scalable framework for matching patients to the therapies most likely to benefit them.

Selected publications:

• Study Tests Targeted Drugs for Multiple Myeloma. Cancer Discov 1 April 2019; 9 (4): 459.
  

The MyCheckpoint study is a key component of the MMRF’s efforts to advance immunotherapy for multiple myeloma. Focused on the promise of checkpoint inhibitors—agents that have transformed treatment for many solid tumors—this trial investigates how these therapies can be leveraged in the context of multiple myeloma (ClinicalTrials.gov identifier NCT04150965).

The study aims to:

• Evaluate two checkpoint inhibitors in multiple myeloma
• Conduct laboratory studies to define their mechanisms of action within the myeloma immune environment
• Understand the pathways myeloma cells use to evade immune detection in order to design therapies that can overcome these escape mechanisms

By integrating clinical evaluation with mechanistic laboratory research, MyCheckpoint helps uncover the immunologic vulnerabilities of multiple myeloma and lays the groundwork for developing future immunotherapy approaches. This work supports the MMRF’s commitment to driving the next generation of therapeutic innovation in multiple myeloma.

Selected publications:

• Richard S., et al. Nature Cancer 2024
  

The MMRF MPP study—also known as Clinical-grade Molecular Profiling of Patients with Multiple Myeloma and Related Plasma Cell Malignancies—is a foundational initiative designed to comprehensively profile the bone marrow of patients with multiple myeloma and related plasma cell disorders. Unlike therapeutic trials, this study focuses on high-quality tissue collection, clinical-grade genetic sequencing, and the creation of a robust clinical database to support basic, translational, and clinical research.

The study aims to:

• Provide clinical-grade genetic sequencing to patients with multiple myeloma and related conditions such as smoldering myeloma, MGUS, primary plasma cell leukemia, solitary plasmacytoma, and amyloidosis
• Correlate biospecimen-derived molecular data with detailed clinical information to enable biomarker discovery and support precision-medicine approaches

By integrating high-resolution molecular profiling with longitudinal clinical outcomes, the MPP study establishes an invaluable resource for biomarker development, disease characterization, and the testing of precision medicine in multiple myeloma and related plasma cell malignancies.

Selected publications:

• Vo JN, et al. Nature Communications 2022
  

The MMRF TRU—Translational Research Umbrella—program is a major effort to expand molecular, cellular, and immune profiling in relapsed multiple myeloma to address critical scientific questions surrounding new and emerging therapies. By generating deeply characterized datasets from patients treated in the real world, the TRU program aims to identify the biological determinants of therapeutic response, inform the development of next-generation treatment strategies, and accelerate the movement of the most promising therapies into earlier lines of care.

The first substudy within this initiative, TRU-1, will launch in 2025 and focuses specifically on patients receiving BCMA-directed therapies. TRU-1 is designed to dissect the mechanisms that shape patient outcomes following bispecific antibody or CAR-T treatment, including the interplay between tumor biology, the immune microenvironment, and the microbiome.

TRU-1 aims to:

• Identify key cellular and molecular factors that determine response and resistance to T-cell–redirecting therapies
• Enable rational design of immune treatment strategies that maximize efficacy and reduce toxicity
• Position T-cell redirection therapies for broader, more effective clinical application across the myeloma population

The TRU-1 substudy will enroll approximately 150 patients receiving BCMA-directed bispecific antibodies or CAR-T therapy as standard of care. The study will collect blood, tumor, tumor-microenvironment, and microbiome samples at baseline, throughout therapy, and at relapse. By integrating these multimodal datasets with clinical outcomes, TRU-1 will offer a detailed view of each patient’s tumor and immune ecosystem, ultimately guiding the optimal use and future development of T-cell–redirecting therapies.