publication date: Feb. 10, 2017
MMRF contributes largest disease-specific cancer genome dataset to NCI’s Genomic Data Commons
By Matthew Bin Han Ong
It took the Multiple Myeloma Research Foundation nearly a decade and over $40 million to create what the foundation describes as the largest disease-specific cancer genome dataset in existence.
The first installment of the dataset is now posted on NCI’s Genomic Data Commons, which places the information in the public domain, making it available to researchers.
When MMRF learned of NCI’s efforts to build the central repository of cancer genomic data, the foundation decided that MMRF would become the first nonprofit research foundation to contribute data.
“There are 38 other cancers on the GDC site, and multiple myeloma is now the largest by far, given this data contribution. One of the things we’re very proud of is that we are the first research foundation to contribute data to the GDC,” Paul Giusti, MMRF president and CEO, said to The Cancer Letter. “Our hope is that this will inspire other nonprofits and research foundations to look at the GDC as a common data aggregation site where we can all place data and be able to provide it to researchers to access.”
The MMRF was established in 1998 by twin sisters Kathy Giusti and Karen Andrews, after Kathy was diagnosed with the blood cancer. In the 90s, no treatment had been developed for multiple myeloma in decades, and what was available wasn’t very effective.
Kathy ran the MMRF for the first 17 years and created the CoMMpass study, a $40 million longitudinal effort that has conducted full genome sequencing of almost 1,200 multiple myeloma patients at the time of diagnosis. This information is now a part of the GDC.
Since 2003, FDA has approved 10 new multiple myeloma drugs—averaging about one every 18 months.
In 2015 alone, FDA approved four drugs that had received support from MMRF. One of them was Farydak (panobinostat), a Novartis agent, and the first histone deacetylases (HDAC) inhibitor approved to treat multiple myeloma.
The other three drugs, approved in a single month—November 2015—are:
Darzalex (daratumumab), sponsored by Janssen Biotech, became the first human anti-CD38 monoclonal antibody approved for multiple myeloma,
Empliciti (elotuzumab), also a monoclonal antibody sponsored by Celgene, and
Ninlaro (ixazomib), a proteasome inhibitor sponsored by Takeda Pharmaceuticals.
“We have always been advocates of getting data into the public domain as quickly as we can,” Paul Giusti said. “In our conversation with Lou Staudt [director of the NCI Center for Cancer Genomics], he was very interested in having a nonprofit foundation that has such well-curated data get that into the GDC. We were very excited about working with him to make that happen.”
Paul Giusti took over as president and CEO of MMRF in February 2016, when Kathy was appointed chair of the Harvard Business School (HBS) Kraft Precision Medicine Accelerator, a bioinformatics initiative designed to speed medical breakthroughs in precision medicine. It convenes best-in-class leaders to identify and solve challenges slowing the advancement of precision medicine, disseminate best practices and models to overcome these challenges, and, ultimately, enable the faster commercialization of high-impact innovations.
“The MMRF participated in a meeting as part of the Kraft Precision Medicine Accelerator in June where one of the big topics that we talked about was data sharing,” Paul Giusti said. “The Kraft Accelerator’s goal is to accelerate precision medicine so it certainly helped to move this along.”
The MMRF, located in Norwalk, Conn., is contributing patient data from over 1,400 cases to the GDC.
“All of [MMRF data] is in the real world, it isn’t just a clinical trial with a couple of arms, and this is why it’s so exciting,” Paul Giusti said. “The database is very well curated and very well organized, and it’s the gold standard of myeloma data.”
The GDC is NCI’s latest Big Data effort in consolidating its separate cancer databases into one portal that researchers can access to download and study raw genomic data (The Cancer Letter, April 29, 2016).
During its launch, the $20 million initiative received a high-profile endorsement in June 2016, when Vice President Joe Biden called it the “foundational element” in building a knowledge network for cancer and the National Cancer Moonshot Initiative (The Cancer Letter, June 10, 2016).
A month later, Foundation Medicine announced it would contribute 18,000 cases, increasing the GDC’s genomic information from 14,500 patients to 32,500 (The Cancer Letter, July 29, 2016).
The GDC is a core component of the Cancer Moonshot and the President’s Precision Medicine Initiative, and it benefits from $70 million allocated to NCI to lead efforts in cancer genomics as part of the initiative.
According to NCI, multiple myeloma is the second most common blood cancer, but large amounts of genomic data about this disease and other cancers have not been readily accessible to researchers.
“Data-sharing is essential to advancing cancer research, and I cannot overstate the value of the data that MMRF is providing—not only genomic data, but also full clinical data,” said NCI Acting Director Doug Lowy. “Combining genomic and clinical information will create an invaluable resource for all researchers worldwide studying this disease who are working toward new, more effective treatments.”
NCI hopes other disease groups will share their data
MMRF’s contribution draws data from its Multiple Myeloma Genomics Initiative and CoMMpass study.
The MMGI, a progressive genome-mapping program, was launched in 2005 to molecularly profile 250 relapsed and refractory patients, with the goal of accelerating targeted therapies for specific subgroups. Through this initiative, whole genome sequencing of the myeloma genome was completed for the first time.
The CoMMpass study, also known as the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (NCT01454297) study, is a an eight-year study partnership between more than 70 academic and community centers, four pharmaceutical companies, and the Department of Veterans Affairs.
African Americans represent about 18 percent of the patients enrolled CoMMpass, based on an interim analysis. The participation of African Americans in this study is significant, given that multiple myeloma occurs about twice as often in blacks than in whites.
Over the next eight years or longer, patients in CoMMpass will get a repeat biopsy and a new genomic analysis at each six-month checkup or at disease progression. Tumor samples are being collected and analyzed when possible at the time of any relapse. The genomic data from these analyses will be immediately deposited in the GDC, with an anticipated sample size of near 1,000 cases by the spring of 2017. New data will be deposited every six months at a minimum.
CoMMpass is the largest single-disease genomic database in any cancer. Moreover, it has follow-up to track trends and progress, Giusti said.
“Our hope is, someday, that you’ll be able to look at their genomic information, their profile, at the point of diagnosis and be predictive about whether they were high risk, whether they’re going to be great responders to treatment, and what treatments are they responding best to,” Giusti said.
The MMRF contribution to the GDC is noteworthy for its scope and potential to provide new insights into the pathogenesis and treatment of multiple myeloma, said NCI’s Staudt.
“The GDC currently has no genomic data from patients with multiple myeloma, so this will dramatically expand the GDC into the realm of lymphoid malignancies,” Staudt said The Cancer Letter. “The size of the MMRF dataset is so large that most researchers studying multiple myeloma are unable to analyze the raw data on their own.”
The GDC will allow researchers to browse the data and make discoveries within the GDC environment, and then download only the subset of the data that is useful for their research.
“Data from whole genome sequencing, exome sequencing and/or RNA sequencing will be available on over 1,000 patients, which is coupled to comprehensive clinical data regarding disease status at regular intervals and response to therapy, “Staudt said. “We expect that the GDC will facilitate precision medicine approaches to multiple myeloma by enabling discoveries regarding genomic correlates of treatment response or resistance.”
The GDC site continues to have many visitors each day, Staudt said, and NCI is getting inquiries about new submissions to the database. Among these are many users who have privileges to view controlled access TCGA and TARGET data.
“The MMRF data donation to the GDC is a remarkable step by a non-profit patient advocacy group to accelerate cancer research,” Staudt said. “We hope that this decision by the MMRF will lead other such cancer advocacy groups to share their genomic and clinical data through the GDC.”
MMRF will continue to aggregate data and build on the CoMMpass database, Giusti said.
“We need to innovate in clinical trials to speed the process,” Giusti said. “This includes work in using minimal residual disease (MRD) as a surrogate endpoint for clinical trial design.
“With 10 new drugs approved by the FDA to treat multiple myeloma in the past 10 years, we need to better understand which drugs in which combinations are most efficacious for each patient.”