15 Years, 1,143 Patients, Hundreds of Breakthroughs: How CoMMpass Transformed What We Know About Myeloma

The Multiple Myeloma Research Foundation looks back on 15 years of the CoMMpass Study’s impact.

When the Multiple Myeloma Research Foundation (MMRF) launched the CoMMpass^SM Study in 2011, it set out to do something unprecedented for a cancer as uncommon as multiple myeloma. CoMMpass would enroll more than 1,000 newly diagnosed patients over four years, sequence their myeloma genomes, track their outcomes for eight or more years, and share its data with the rest of the field.

“The MMRF CoMMpass Study is the single most important thing going on in the myeloma world,” said David Siegel, MD, PhD of Hackensack University Medical Center early on.

Fifteen years later, the MMRF’s audacious bet has become one of the most complete molecular portraits of any cancer, and CoMMpass is now widely considered to be the most valuable dataset in myeloma. To date, more than 3,000 researchers have accessed CoMMpass data and used it in more than 700 publications.

Here, the MMRF looks back on CoMMpass’ impact in myeloma over the last 15 years, along with what’s to come.

A study rooted in collaboration and access

From the start, CoMMpass was designed to be different from almost every other study in myeloma. It paired a longitudinal structure—where the same patients were followed over years—with robust data collection that hadn’t been seen in myeloma at this scale.

The 1,143 newly diagnosed patients who enrolled in CoMMpass were followed for at least eight years and consented to bone marrow and blood sampling across several moments in their myeloma journey: at baseline, remission, and relapse. In 2023, follow-up was completed for the final cohort of enrolled patients.

To achieve this massive undertaking and the genomic sequencing of all available samples, the MMRF brought together academic, industry, and other partners that are sometimes seen as competitors. Ultimately, this provided a blueprint for large-scale collaborative cancer research. In total, 76 medical centers across North America and Europe enrolled patients into the CoMMpass study.

The MMRF made two additional innovative decisions: The data would be shared publicly, and it would be shared at regular intervals before study completion. Most studies only share data at the end, and the data is often held only by the team that did the work.

These decisions, along with the scale and structure of CoMMpass, led to a steady stream of published discoveries that have transformed myeloma from a poorly understood disease into one of the most deeply characterized cancers.

New insights into myeloma risk

CoMMpass data helped reshape the field’s understanding of risk by revealing that it is not defined by a single marker, but by combinations of genetic features and how they interact. Thanks to CoMMpass, we now know that some features once considered high-risk on their own are only significant in the presence of other features. At the same time, some high-risk patients are missed by standard risk assessments, highlighting the need for more precise risk modeling.

For example, CoMMpass data identified an ultra-high-risk form of myeloma known as “double‑hit” myeloma that occurs in about six percent of patients. These patients have a specific combination of genetic alterations, including a complete loss of both copies of the TP53 gene and other chromosomal changes, that together, cause a particularly aggressive form of myeloma. While some of these alterations can be detected individually, the combinations that make them ultra-high risk are not fully captured by traditional risk assessments.

In 2024, the MMRF and its collaborators published a landmark analysis of the full CoMMpass cohort in Nature Genetics. Drawing on data from all 1,143 patients in the study, researchers offered the most complete picture yet of how myeloma progresses from a treatable condition to a high-risk state—and, for the first time, proved that the rate at which patients transition to a high-risk subtype could be measured. It proved what CoMMpass data had suggested for years: that a patient’s risk level isn’t fixed at diagnosis but can and does change as the disease progresses.

CoMMpass data has also been used to demonstrate that, for patients who can access them, next-generation sequencing methods can more precisely predict risk than standard methods.

These findings and others from the CoMMpass dataset helped lay the groundwork for the new consensus definition of high-risk myeloma that was recommended by the influential International Myeloma Society (IMS) and the International Myeloma Working Group (IMWG) in 2025.

Advancing new treatments for myeloma

Identifying new myeloma subtypes and high-risk features only matters if those insights change how patients are treated. From the beginning, CoMMpass was built to harness genomic discoveries and turn them into new therapies and improvements in care.

For example, CoMMpass data was used to confirm findings showing that autologous stem cell transplant was superior to traditional treatment approaches like chemotherapy, helping make it the standard of care.

The MMRF’s clinical research subsidiary, the Multiple Myeloma Research Consortium® (MMRC®), launched the first genomically-guided platform trial for myeloma, MyDRUG, based on discoveries in the CoMMpass dataset. MyDRUG aimed to match patients to targeted therapies that were approved for other cancers based on specific features of their disease. The MMRC then built upon learning from the MyDRUG trial to launch the groundbreaking Horizon platform trials in 2024.

CoMMpass’ scale has also been an asset for clinicians treating individual patients and especially those with rare genetic features. Some have been able to identify patients with similar characteristics in CoMMpass and tailor treatment based on the data.

Revealing myeloma’s complexity

Very early MMRF research suggested that myeloma was highly heterogeneous, but the field lacked data that showed when and how the disease evolved during a patient’s treatment journey. Over the years, researchers have leveraged CoMMpass data and advanced sequencing technology to not only demonstrate that myeloma is highly heterogeneous, but to identify 12 distinct genomic subtypes of the disease that could be further studied.

“By repeatedly sampling patients across their myeloma journey, CoMMpass gathered vast amounts of data about how myeloma evolves, what new mutations emerge over time, and how patients develop drug resistance,” said George Mulligan, PhD, MMRF chief scientific officer. “This helped evolve the field’s understanding of myeloma from a static disease to an evolving one.”

One of CoMMpass’ distinguishing features was its commitment to enrolling a patient population that closely mirrors the real-world myeloma community. Because of that, researchers can be more confident that the insights from CoMMpass apply to the broader myeloma population, unlike findings from other similar studies, which tend to enroll more homogeneous groups of patients. This representative dataset helped uncover important biological differences across racial groups and showed that, when patients receive the same treatments, survival outcomes are comparable across races—highlighting the critical importance of equitable access to high-quality care.

Mapping patients’ immune systems

In 2019, the MMRF launched its Immune Atlas project to define the immune microenvironment and its role in myeloma. From 2020–2023, the MMRF and its collaborators at five leading academic medical centers used bone marrow and blood samples from CoMMpass to conduct sophisticated immune profiling at the time of a patient’s diagnosis and during their disease journey (after stem cell transplant or at treatment response or relapse).

Earlier this year, the MMRF and its partners published two important studies from its Immune Atlas data. These papers offered important new insights into the immune system’s role in myeloma—and once again demonstrated the value of the MMRF’s collaborative model and datasets like CoMMpass. Over the coming years, Immune Atlas investigators expect to share more results and insights as they continue to analyze this data.

Building on CoMMpass’ impact

To further extend the reach of its datasets, the Foundation recently launched the MMRF Virtual Lab®, the largest and most comprehensive data-sharing platform in multiple myeloma. Virtual Lab now houses all the data the MMRF has generated across its landmark research projects, including the final genomic and clinical data from CoMMpass.

By continuing to make this data available to researchers around the world—as the MMRF has done for the last 15 years—but in a more sophisticated platform with built-in analytical tools, CoMMpass data will remain as relevant as ever.

CoMMpass has done more than deepen our knowledge of myeloma and prove that the disease could be studied at remarkable scale. It changed how the entire field works, with many myeloma researchers turning to CoMMpass data every time they have a new idea or hypothesis to test.

“CoMMpass is more relevant today than it was when we first embarked on it,” says CoMMpass principal investigator Sagar Lonial, MD of Emory University. “When we’re doing an analysis or something new in myeloma, the first question is always: Well, what does CoMMpass say about this?”

Today, CoMMpass continues to generate new insights, and the model it pioneered now extends well beyond its original design. For the MMRF, it’s a foundation to keep building on toward our ultimate goal: a cure for every myeloma patient.