In an interview with Targeted Oncology, Hearn Jay Cho, MD, PhD, Chief Medical Officer of MMRF and Associate Professor of Hematology and Medical Oncology at Mount Sinai Hospital Ruttenberg Treatment Center and Irene M. Ghobrial, MD, Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School discussed the importance of the CureCloud study for the multiple myeloma community and their hopes for what this study can achieve for myeloma patients and their physicians.
TARGETED ONCOLOGY: Can you explain what the MMRF CureCloud is? Who is the sponsor and who wrote the protocol for the study?
Cho: MMRF CureCloud is a clinical trial, which is sponsored by the Multiple Myeloma Research Foundation. CureCloud is open to any patient with multiple myeloma, except for patients living in Hawaii and Alaska, where lengthy shipping time prohibits a successful sequencing test, and New York, which requires additional laboratory certifications, which we are currently working on, but have not completed at this time. Eligibility requirements also include an M-spike value of 0.3 g/dL or greater and a free light chain ratio (involved/uninvolved) of 8 or more.
The intention is to provide information back to the patient about their disease and to amass patient data. This will be real-world data collected in a longitudinal fashion for approximately 5000 patients with multiple myeloma. The protocol was developed in a collaborative effort between the research, clinical, and data teams at the MMRF.
TARGETED ONCOLOGY: What goes into participating in CureCloud for both patients with multiple myeloma and physicians, and what information do they receive?
Cho: The intention of this project is to bring information of value directly to patients. A patient with myeloma can go online, review the information about the project, enter their M-spike and kappa/lambda data to confirm their eligibility, review the consent form, and sign it online. That triggers a process where an order for a blood draw from the patient is provided. The patient can then go to their treating physician and get the order signed. When a signed order is received by the MMRF, this triggers two processes related to the blood draw. First, a blood kit is sent to the patient’s home, and a blood draw is scheduled. A mobile phlebotomist will go to the patient’s home, take blood samples, and send those samples back to the MMRF.
Part of the sample goes to our collaborators at the Broad Institute in Boston. There, the sample will be subjected to a cell-free DNA assay that will sequence 70 genes related to cancer and relevant to multiple myeloma. Another sample goes to our tissue bank where it’s stored for potential future use in other types of laboratory assays.
Second, the signed consent form allows us to access the patient’s electronic medical records at all institutions where they receive medical care, and we will collect these clinical data and combine them with the genomic data obtained from the 70-gene assay at the Broad Institute.
Also, the protocol is designed to add future cassettes of data. If in the future immunologic assays are performed on the stored samples or additional data is gathered electronically from the patient’s medical records, these will be added to the database so that we will have a comprehensive store of real-world patient data, in addition to cutting-edge molecular and genomic assay results.
TARGETED ONCOLOGY: What specific information will the report show for both patients and physicians?
Cho: The 70-gene panel, which was designed for our cell-free DNA sequencing assay, are all cancer-related genes, some of which are very commonly mutated in multiple myeloma. The information that is derived from this assay will be provided to the ordering physician in the form of a molecular pathology report from our collaborating pathologists at the Dana-Farber Cancer Institute in Boston. That information will be rewritten for patients in lay person form by a company called My Gene Counsel, which has experience producing patient-level reports on complex genetic information.
In particular, we have identified a group of genes that are commonly mutated in cancers, including multiple myeloma, for which there are certain targeted drugs available that have been approved for use in other types of cancers. In some cases, there are clinical trials examining the activity of these same drugs in multiple myeloma.
What will be reported back to patients is the mutations that have been detected in their blood and if there are clinical trials for which this patient may potentially be eligible based on these mutations. That gives the patient additional options to discuss with their physician in order to find the most appropriate treatment regimens for them.
TARGETED ONCOLOGY: How do you think this will help guide treatment decision making?
Ghobrial: We’re now in the era of precision medicine, and I think the first example of that is venetoclax [Venclexta]. It’s a drug that specifically works on a subset of patients who have t(11;14) translocation or have a high BCL-2 level. And we know that there are so many other aberrations that will have specific treatment [associations]. We know, for example, if [a patient has] high-risk cytogenetics, we want to treat [these patients] specifically with certain drugs or be more aggressive in our treatment versus someone else who has better prognostic markers we may not want to push too much with the treatment. So altering treatment based on what we understand from the biology is very important. And we always say that multiple myeloma is truly multiple types of myeloma, and we shouldn’t expect to treat all patients the same way.
TARGETED ONCOLOGY: What if the patient does not have any actionable alterations?
Cho: There is a possibility that there may be no mutations detected in a patient’s blood that can be specifically targeted. In those cases, we will not recommend any clinical trials.
TARGETED ONCOLOGY: This test appears to be offered free for patients. How is it that the MMRF is able to offer this test for free?
Cho: The MMRF is the sponsor of this protocol, and we have committed substantial funds in order to provide these tests to the patient free of charge. We’re covering the cost as part of the research program.
TARGETED ONCOLOGY: Tell us more about the CureCloud assay. What method of sequencing does it use and what is it looking for? What does this mean for CureCloud and the future of liquid biopsies for multiple myeloma in clinical practice?
Cho: The CureCloud assay is the first liquid biopsy for multiple myeloma. It is a CLIA [Clinical Laboratory Improvement Amendments]–certified assay that was developed in collaboration with our colleagues at the Broad Institute. This is a cell-free DNA assay, so DNA that was released by cells, including cancer cells, is isolated from the peripheral blood, and those pieces of DNA are sequenced using probes that are specific to 70 common cancer-associated genes. These probes will provide sufficient depth of sequencing that we will be able to [identify] mutations, with confidence, if they are present in some of the genes that are detected.
The raw data from this assay are sent to our colleagues at the Dana-Farber Cancer Institute in the Department of Molecular Pathology. These data are interpreted so that a report can be generated detailing the specific mutations detected in these specific cancer-associated genes. This is a first-of-its-kind liquid biopsy specifically tailored for multiple myeloma that will return this important information to the patients and their treating physicians.
TARGETED ONCOLOGY: What can you tell other physicians about why their patients should participate in CureCloud?
Cho: We’re trying to return what we’ve learned to the patients. In previous studies, such as the CoMMpass study (NCT01454297), which enrolled over 1000 newly diagnosed patients with multiple myeloma, we learned an enormous amount about the genomics of multiple myeloma. We learned how it drives the disease, and in particular, we discovered that certain genes, which are commonly mutated in other cancers, are commonly mutated in multiple myeloma as well.
We wanted to be able to provide this information to patients, even if they’re not being treated at an academic medical center or in a big, academic multiple myeloma program. So this is for patients who are being treated by community physicians who don’t necessarily have access to this cutting-edge technology.
We are bringing the discoveries that we made in the laboratory directly to patients so they can learn more about their disease and so they can have more informed, data-driven discussions with their providers about treatment decisions.
Ghobrial: In general, patients with multiple myeloma want to know what their underlying genetics are. They want to know what is going on with them so that they can have a better sense of which treatment option would be best for them.
Currently, we do [tests] on the bone marrow biopsy. CureCloud is taking it to the next step with liquid biopsy. It’s much easier for patients compared with bone marrow biopsy, and it’s taking it to something called next-generation sequencing. Instead of looking at the big pieces of chromosomes with FISH [fluorescence in situ hybridization] and cytogenetics, we now can truly look at specific mutations and copy number alterations and make better decisions for patients based [on data]. That’s the power of CureCloud, taking it to the next step of precision medicine.
TARGETED ONCOLOGY: Once enough data have been received, how can patients and physicians access and use the aggregated data sets?
Cho: When patients enroll in this study, [they’re given access to] a personal web portal. In addition, the physician who signs the order form for the liquid biopsy has access to a physician portal. The data that are generated by the biopsy are made available to the treating physician through that portal. The patients also receive an interpreted report from My Gene Counsel. These will all be dynamic documents. In the future, as more information is added to CureCloud, we will be able to provide overview information about patients who are participating in CureCloud.
To read the full interview click here.