MMRF CoMMpass Study: An Update

For myeloma patients and their caregivers, the fast-growing number of treatment options can be overwhelming. The importance of staying current on new developments in myeloma research and treatment has never been greater.

Increasingly, the focus for myeloma researchers and doctors has been on the development of treatments that can be personalized to each patient based on the patient’s genetics. A big part of this effort is the MMRF CoMMpass Study, a major research project in which more than 1,100 patients with newly diagnosed active myeloma are being tracked over a period of 8 years. This study collects information about what treatments each patient receives, how long the treatment is given, how well each treatment works, whether patients received a stem cell transplant, and much more.

Another important—and, indeed, groundbreaking—aspect of the CoMMpass Study is that all participants undergo a type of detailed genetic testing called genomic sequencing. Blood and bone marrow samples are taken when a person first enters the study, when he or she has a response to treatment, and when the myeloma relapses. The detailed genetic information from these samples helps the CoMMpass researchers identify new mutations or molecular changes that can help promote survival and growth of myeloma cells, contribute to treatment resistance, and help predict a patient’s response to therapy. This information also enables the researchers to compile detailed molecular profiles for every myeloma patient in the study, and this has helped reveal that there are actually several (the current count is 12) subtypes of myeloma. These different subtypes respond differently to different treatments, so the ability to identify which subtype of myeloma a patient has greatly increases the health care team’s ability to choose the treatment approach that will be most effective.

Some of the important discoveries relating to multiple myeloma subtypes that have emerged from the CoMMpass Study include the following:

  • One subtype is characterized by the inactivation of the TP53 Normally, people have two copies of the TP53 gene, which are found on chromosome 17. When both copies of TP53 are nonfunctional, it is an example of what is referred to as double-hit multiple myeloma—a category of myeloma associated with shorter survival. The ability to identify patients with double-hit myeloma, using the same genetic tests used by the CoMMpass researchers, provides the health care team the opportunity to use innovative therapies (for example, chimeric antigen receptor T-cell [CAR T-cell] immunotherapy) to improve outcomes for these patients.
  • Another myeloma subtype was found to involve a type of genetic abnormality called a chromosomal translocation. In this case, the specific abnormality is called t(IgL), and it is found in about 10% of myeloma patients. Among other important findings regarding these patients, it has been determined that they do not benefit from treatments that include immunomodulatory drugs (such as Revlimid). Determining whether patients have this myeloma subtype can help doctors more quickly and more effectively identify more suitable treatments.
  • The genetic information revealed in the CoMMpass study may also help identify patients who may be resistant to certain treatments. One particular gene (called myeloid cell leukemia-1 or MCL-1), which helps to promote the survival of cancer cells, is mutated at a high frequency in myeloma patients. Inhibitors of MCL-1 are currently being developed and studied in clinical trials, so the discovery that MCL-1 gene mutations make myeloma cells resistant to these drugs has important implications for treating patients with this mutation.

Besides identifying genetic features in specific subgroups of myeloma patients, the CoMMpass Study has made other important contributions to myeloma patient care. For instance, the CoMMpass Study showed that measuring the circulation of myeloma cells in the blood can be a useful tool to monitor how the cancer is behaving and to estimate a given patient’s likelihood of responding to a particular treatment. Thus, the CoMMpass researchers developed an automated method for counting and analyzing multiple myeloma cells in the blood and found that patients with less than 100 circulating myeloma cells at remission had greater survival benefits than did patients with more than 100 circulating myeloma cells. This noninvasive way of following the biological behavior of myeloma provides clinicians a window into the progression of myeloma over time and across treatments.

Have all subtypes of multiple myeloma been identified? Are we now able to personalize treatment to every myeloma patient? Though the molecular and genetic discoveries achieved thus far in the CoMMpass Study have provided a truly amazing boost to the advancement of myeloma patient care, the job will never be complete until the last myeloma patient is cured. So the work will continue.

The findings of the CoMMpass Study are moving us closer to the goal of personalizing treatment to every myeloma patient and have provided invaluable information that is guiding treatments in larger studies, such as the MyDRUG clinical trial launched by the MMRF. Patients enrolled in this trial undergo genome sequencing and, based on the changes found, receive treatment that is matched to the drugs or therapies that target their specific unique myeloma subtype.

Nurse Patient Navigators in the MMRF Patient Support Center are always available at 866-603-6628 to help answer any questions you have or to help you find the right resources to help in your fight against myeloma.

Additional Resources

MMRF. 2018 Patient Webinars.

MMRF. ASH 2018 – MMRF CoMMpass Study Findings #2.

MMRF. ASH 2018 Day 2 – CoMMpass Oral Presentations.

MMRF. ASH 2018 Day 3 – Oral CoMMpass ONLY.

MMRF. MMRF Answer Fund: How CoMMpass data is helping define high-risk disease.

MMRF. MMRF CoMMpass Study.

MMRF. MyDrug Study.

MMRF. Precision Medicine.