NORWALK, Conn.—The Multiple Myeloma Research Foundation(MMRF) has announced a partnership with US Oncology Research to undertake alandmark, long-term clinical study of multiple myeloma's (MM) natural historyand its effects on the body at the molecular level.
MM is an incurable cancer of the blood. An estimated 20,000new cases are diagnosed every year, and close to 100,000 patients are currentlyliving with the disease.
According to Dr. Robert Rifkin, oncologist and hematologistat Rocky Mountain Cancer Centers, which is affiliated with US OncologyResearch, 20 years ago, survivability among those diagnosed with multiplemyeloma was very poor—perhaps two to three years.
"Fortunately, during the past couple of decades, we'vegained access to a host of new agents, including proteasome drug classes andstem cell transplants," he says. "We've improved patient survivability to 10 yearsor more in some cases."
Medical science still has a long way to go, however. It hasyet to be able to fully analyze the natural history of MM. Part of what makesthe disease so difficult to understand and treat is the fact that it arisesfrom multiple malignancies rather than from a single illness or event—forexample, toxic exposure followed by an infection. The combination of factorsleading to the development of the illness varies from patient to patient,making a one-size-fits-all therapy that much more difficult to isolate.
Instead of looking for a single new therapy, thiscollaboration between MMRF and US Oncology Research will be a foray intopersonalized medicine, with the hope of learning the molecular and geneticchanges that mark the progression of the disease and discovering ways to catertreatment to each individual case. This landmark study has been dubbed RelatingClinical Outcomes in Multiple Myeloma to Personal Assessment of GeneticProfile, or CoMMpass, and is supported by a $40 million investment by the MMRF.
"This study is really a prototype of personalized medicine,"says Dr. Carolyn Hoban, director of translational research at MMRF. "Theresults may someday empower physician's decision-making regarding treatmentoptions for their patients."
"Our goal is to accrue 1,000 newly diagnosed multiplemyeloma patients and to use genome sequencing to identify new targets fortherapy, which could potentially lead to the development of a new drug," saysRifkin. "We would then be able to take it through development. We plan tofollow the patients for a minimum of five years."
At the outset, newly diagnosed MM patients' tissues will beanalyzed for quality and whole-genome sequencing. Their chromosomes will beanalyzed, and DNA and RNA samples will be extracted as they begin therapy.Researchers will be able to observe these patients going forward and returninformation in real-time, both to the doctors and to the patients. Finally,additional sets of tissue samples will be taken at each relapse and at the timeof failure of treatment, providing benchmarks that will allow researchers toobserve the molecular-level changes that have occurred during the course of thedisease.
The study also aims to create a "biobank" of serum andplasma that can be further analyzed to look for better biomarkers to facilitatenew diagnostic and treatment options in future patients.
"We hope to discover more noninvasive diagnostic tools thatwill minimize the discomfort to the patient," Hoban says.
The collaboration between MMRF and US Oncology Researchmarries two robust partners in the fight against multiple myeloma. US OncologyResearch represents a large community of MM patients and physicians, as theorganization sees roughly 20 percent of all new MM cases, and has participatedin 38 out of 40 U.S. Food and Drug Administration (FDA)-approved drugs. USOncology Research is already currently involved in about 100 other open trials,and will be the principal investigator overseeing the CoMMpass study. Aside fromfinancial sponsorship of the CoMMpass study, the Multiple Myeloma ResearchFoundation brings to the table the technology and the science necessary toprocess the tissue samples and conduct the genome sequencing and othermolecular analyses.
The CoMMpass study already has two pharmaceuticalpartners—Millennium and Onyx—that, in exchange for financial support of thestudy, will receive priority access to the data it generates for a six-monthwindow, after which the data will enter the public domain. Two or threeadditional pharmaceutical partners may be added to the study later.
"Our hope is that we will quickly begin generatinghypotheses that can lead to clinical trials," says Anne Quinn Young, vicepresident of marketing at MMRF. "We're in a position to play a lead role inconnecting this data to therapeutic advances."
"We need more collaborations like this between the medicaland patient communities and academia," Rifkin says. "We're off to a goodstart."