Greetings from San Diego! We are here covering the Myeloma 2018 meeting. This meeting of 200 top myeloma scientists happens yearly in different locations, and MMRF is here to bring you the highlights.
On day 1, there were several interesting sessions. The meeting opened with a presentation by Dr. Jonathan Keats of the Translational Genomics Institute (TGen) on highlights from the MMRF CoMMpass Study, now the largest genomic dataset in all of cancer. Dr. Keats presented findings from the latest CoMMpass data analysis. For more information on the latest findings, see our latest blog post here.
Blood Biopsies in Myeloma
Next were several presentations on progress made in development of several different techniques that may be used to assess myeloma instead of bone marrow biopsies.
- Suzanne Trudel of Princess Margaret Hospital in Toronto and Jens Lohr of the Dana Farber Cancer Institute in Boston spoke on a technique that measures how much myeloma is present in a patient by detecting tumor DNA from a simple blood sample. This work has been supported by the MMRF. The technique has been under development for several years and hopefully will soon replace the bone marrow biopsy in many instances. The advantages of this technique include:
- Reduced discomfort and risk for patients
- More frequent sampling can be easily done, allowing your doctor to follow your disease more closely
- Since the test measures tumor DNA that is circulating throughout the body, it is possibly a more accurate measurement of disease burden than a bone marrow biopsy, which measures myeloma cells only in one place
- Patient who enroll in and submit their blood samples through the MMRF CureCloud patient registry, which is currently in beta testing and will be open to patients later this fall, will benefit from this technique
- Angela Dispenzieri of the Mayo Clinic Rochester MN spoke on a new method of detecting minimal residual disease (MRD) in blood using the mass spectrometry technique, which measures free light chains. This technique is currently in use at Mayo for routine isotyping (determining if the myeloma light chain type is kappa or lambda) from blood or urine samples and will soon replace the SPEP test, as it is more sensitive and more accurate. The test can also detect 1 myeloma cell in 100,000 cells, which makes it a good alternative to the already available MRD test methods of next generation sequencing and flow cytometry
- MMRF Senior VP of Research Daniel Auclair, PhD, closed the session with a discussion of the upcoming precision medicine trial, called MyDRUG, which will begin enrolling patients later this fall. The trial will enable patients to have their genome sequenced, and they will be treated with a triplet standard of care regimen plus a targeted agent specific to certain actionable mutations if they are found. More information on this ground-breaking trial for myeloma patients will be coming soon!
High Risk Myeloma
The next session brought a presentation by Anjun Thakurta of Celgene on a new definition of high risk myeloma termed “double hit”, which was discovered using CoMMpass Study data and which was recently published. Learn more about this exciting new finding here.
The morning ended with a spirited group discussion of progress so far on precision medicine in myeloma. While there have been several very small studies showing that agents that target specific DNA mutations, such as braf/RAS and FGFR3, can be effective in achieving remission in myeloma, the group agreed that it is very early days for this type of therapy, and much more work needs to be done to prove the utility of such an approach. Providing more of this data and advancing the use of precision medicine in myeloma is the purpose of the MMRF MyDRUG trial (see above).
New Targets in Myeloma
The afternoon sessions began with a discussion of new targets in myeloma. Dr. Ken Anderson of the Dana-Farber Cancer Institute spoke on several very new and promising targets and therapies which are in the exploratory stage.
- One new approach is to vaccinate patients with BCMA, which is a protein found on myeloma cells. This may allow the immune system to detect and kill myeloma cells. Most CAR-T approaches, such as bb2121, also target BCMA.
- A target called PRMT5 is a protein that is strongly expressed in myeloma patients and is a sign of poor prognosis. A new PRMT5 inhibitor called EPZ015666 has shown promise in mouse models of myeloma and this compound may soon move into clinical trials.
Dr. Keith Stewart of Mayo Clinic Scottsdale AZ spoke on his drug-screening platform, where myeloma cells taken from patients are tested in the lab using 500 different drugs to determine which drug may be most effective for treatment. This is work that MMRF has supported since its inception and continues to support.
- To date 125 patient samples have been tested.
- The patients also have their genomes sequenced, and the data is examined to see if there is a correlation between genomic changes and drug sensitivity.
- One drug, APY0201, was effective at very low doses in some patients. The target of drug, PIKfyve, has been investigated in B cell non Hodgkin lymphoma and inhibitors have been effective in some of those patients.
Investigation into this new target will continue, and Dr. Stewart hopes to move PIKfyve inhibitors into the clinic soon to be tested in myeloma patients.
The final session of the day centered around early myeloma, discussing what we know about treating MGUS/SMM patients and how effective these treatments are in preventing progression of early disease to full-blown myeloma. Dr. Elisbet Manasanch of the MD Anderson Cancer Center in Dallas TX, who is an investigator in our MMRF Prevention Project gave an overview of the subject and several ongoing clinical trials:
- The early Quiridex trial where SMM patients were treated with Revlimid/dex vs observation, showed a clear improvement in progression free survival in treated patients
- Another recent trial where SMM patients were treated with 8 cycles of Kyprolis/Revlimid/dex and received 2 years of Revlimid maintenance, is also showing good results, but the trial has not reached its endpoint yet
- A more recent trial PhII trial called Centaurus treated 123 SMM patients with Darzalex for differing periods of time; patients on longer periods of therapy (20 8-week cycles) showed better response than those on a shorter period of therapy (one 8 week cycle)
- The GEM-CESAR study in high risk SMM tested a regimen of KRd induction followed by stem cell transplant and Rd maintenance in 90 patients. 94% of these patients had not progressed at 28 months after beginning therapy
- There is a new personalized vaccine program in the very early stages , where myeloma cells are removed from SMM patients and sequenced to determine genomic changes; this data is used to produce a personalized vaccine for each patients which is administered once a month for 6 months. Results in this study are still pending.
Clearly the benefits of early treatment (delay of symptomatic disease, possibility of cure) must be weighed against the risks (toxicity, cost, possibility of overtreatment).
Tune in again tomorrow for more results from Myeloma 2018!
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