Multiple myeloma (MM) is a highly heterogenous and incurable cancer. As the second most common blood cancer in the United States, the American Cancer Society estimates that 32,270 new cases will be diagnosed with MM in 2020, and an estimated 12,830 people are predicted to die from the disease. According to the Multiple Myeloma Research Foundation (MMRF), the 5-year survival rate for MM is roughly 47 percent versus 31 percent in 1999.
Despite significant advances in the last decade, the complexity of MM presents considerable challenges and remains incurable. A deeper understanding is urgently needed of the molecular, immune, and clinical parameters involved in disease initiation, progression, and response to treatment. It is essential to collect this level of data at the population level to ultimately make precision medicine a reality for patients with MM.
To address this, the MMRF launched CureCloud (NCT03657251), a first-of-its-kind, direct-to-patient research initiative, on July 14, 2020. The registry is designed to be the most comprehensive database of clinical and genomic information from thousands of patients with MM in the first at-home genomic testing program.
CureCloud builds on findings from the landmark MMRF CoMMpass study (NCT01454297). This research evaluated the genomics of multiple myeloma from over 1,100 participants with newly diagnosed active myeloma who are longitudinally followed over a period of 8 years. The study discovered that there are many different subtypes of MM and confirmed several actionable genomic alterations in myeloma. Thus far, the CoMMpass has identified at least eight unique genomic subtypes of myeloma.
The MMRF CureCloud is the next step to find treatments for every patient, regardless of their subtype. Powered by genomic and clinical information, CureCloud aims to push the field of MM toward precision medicine, while democratizing access to next-generation sequencing for patients who may not otherwise have access.
For researchers, CureCloud aims to help them discover new targets for myeloma, treatments for various subtypes of the disease, and hypotheses for clinical trials. For patients, CureCloud aims to provide them with data to have a well-informed voice in their own treatment selection, and their physicians in making more informed, data-driven treatment recommendations.
The study aims to enroll at least 5,000 patients and collect real-world long-term data. Most patients with active MM requiring treatment who are living in the United States are eligible to enroll. Eligibility requirements also depend on the patient's M-spike and/or kappa/lambda light chain values as a surrogate for disease burden. Patients living in New York, Hawaii, and Alaska were not eligible to enroll at the launch of the trial. Additionally, patients with smoldering myeloma were not yet able to register.
In a streamlined process and at no cost to the patient or provider, a patient can register with CureCloud online. Participants will also be authorizing linkage to their electronic medical records information, which is extracted and paired with their genomic data in the secure, CureCloud database—without any personally identifiable information in order to protect privacy.
Next, those who join will receive a blood drawing kit and a visit from a mobile phlebotomist who will draw the blood sample. A portion of the blood sample will be sent to MMRF's tissue bank at the Mayo Clinic for potential future use in other types of laboratory assays.
For the CureCloud analysis, a portion of the blood sample will go to the MMRF's collaborator, the Broad Institute of MIT and Harvard. There, the cell-free DNA blood samples will be tested to identify common and potentially actionable somatic mutations using a unique, 70-gene panel, with data derived from the CoMMpass study. The study uses a novel, clinical-grade liquid biopsy next-generation sequencing assay specifically developed for MM.
Both patients and their physicians will receive a detailed report on their genomic findings within 4-8 weeks of testing. The patient report will be written in digestible, easy-to-understand language. The physician report includes a breakdown of potentially actionable somatic alterations and professional comments from a molecular pathologist, along with a list of available clinical trials.
Importantly, utilizing CureCloud's unique direct-to-patient concept visualized in a portal, physicians and patients will be able to explore the database and find other patients who share similar defined clinical and/or genomic characteristics to advance data-driven treatment decision-making. In this way, CureCloud has the ability to make precision medicine a reality for the MM community.
Oncology Times checked in with Hearn Jay Cho, MD, PhD, Chief Medical Officer of MMRF, for the latest update on the CureCloud Research Initiative.
The MMRF CureCloud Research Initiative uses a clinical-grade liquid biopsy next-generation sequencing assay for MM. Why is the use of a liquid biopsy assay such a critical aspect of this project and a win for the myeloma community?
Cho: “The gold standard diagnostic test for MM is a bone marrow biopsy and aspiration, which is used for both regular pathology and molecular tests such as tumor genomic sequencing. For many patients, this procedure can be very uncomfortable or painful. It would be ideal to have a similar test that can be performed on a peripheral blood sample, which would be much easier and less painful. The MM-70 liquid biopsy is a big step towards that goal. It is the first CLIA-grade peripheral blood genomics test tailored for MM. It assesses a range of cancer-associated mutations that were identified in the MMRF CoMMpass Study, which enrolled over 1,000 newly diagnosed myeloma patients starting in 2011 and is ongoing.”
The cell-free DNA assay uses a 70-gene panel of common cancer-associated genes. If more genes are discovered that are implicated in multiple myeloma during the study, are there any plans to change the panel or add genes to the panel during the study?
Cho: “Yes. We plan to improve or add better assays as they become available. We are working with our collaborators and are constantly on the lookout for new technology developments for this purpose. We are banking samples from each blood draw so these may be applied retrospectively, if possible.”
The study aims to enroll 5,000 patients within 5 years. How many patients have enrolled thus far? Has there been any unforeseen obstacles in the enrollment process?
Cho: “The biggest obstacle so far has been the COVID-19 pandemic, which has drastically affected every level of operations. It has slowed delivery of kits to patients, scheduling of blood draws, delivery of samples, testing, and report generation. Despite this, the commitment and enthusiasm of the myeloma community has yielded remarkable results. We opened July 14, 2020, and projected about 55 enrollments per month. To date (mid-November), we have 300 fully enrolled subjects with more coming through the registration process, so we are well ahead of schedule.”
At the launch of the study, patients with active multiple myeloma living in New York, Hawaii, and Alaska were not eligible to enroll. Are there any updates for patients living in these states?
Cho: “We could not include Alaska and Hawaii in the launch because we have not yet identified a practical shipping solution that guarantees delivery of the specimens to our testing laboratory in the right time frame. New York State has very stringent requirements for certification of laboratories that perform medical tests, and at launch our collaborating laboratory did not have that certification in place. We are working to solve both problems so we can make CureCloud available to all patients in the U.S.”
Additionally, at the launch, CureCloud was open only to eligible patients with multiple myeloma. For example, patients with smoldering myeloma were not yet able to register. Are there plans toward future expansion of the study to include a broader patient population?
Cho: “This is a very timely question. We are happy to announce a collaborative agreement with the PCROWD/PROMISE study team at the Dana-Farber Cancer Institute in Boston, led by our colleague Irene Ghobrial, MD. Through this collaboration, we will enroll 500 smoldering myeloma patients into CureCloud starting in December 2020.”
What is the long-term vision of the MMRF CureCloud Research Initiative?
Cho: “MMRF CoMMpass was the first comprehensive, longitudinal genomic and clinical assessment of the myeloma population. It is the foundation for so much work in precision medicine and translational research in our field. We are expanding into the immune landscape in MM with Immune Atlas, in which we are performing state-of-the-art immune profiling of bone marrow and blood samples from the CoMMpass tissue bank.
“One of the important lessons from CoMMpass was that there are many genomically defined subtypes of myeloma, much more complicated than the classifications by older technologies such as cytogenetics and fluorescence in situ hybridization (FISH), and some of the critical, high-risk populations are relatively rare. We calculated that we need about 5,000 patients in order to have statistically useful data on the entire spectrum of myeloma, which was the impetus for CureCloud.
“We are gathering research and clinical information now, with plans to add immune and other types of data, to create a comprehensive database that will drive myeloma research for the next generation of therapies and, ultimately, lead to curative treatment for all myeloma patients.”
Dibash Kumar Das is a contributing writer.