Whatever happened to measles vaccine therapy? A status report
Almost two years ago, I wrote about encouraging new research on virus or “viro” therapy for myeloma. Stacy Erholtz, a 50-year-old myeloma patient at the Mayo Clinic, had a dramatic response when treated with a massive dose of engineered measles virus—a dose of measles virus sufficient to vaccinate 10 million people. Stacy continues to do very well at the present time.
There was thus keen interest when, on March 18th 2016, Profectus BioSciences, Inc. announced that it will combine with Vyriad to collaborate in the areas of engineered virus vaccines, most specifically rVSV (recombinant vesicular stomatitis virus), an alternative to the measles virus approach. Stephen J. Russell, MD, PhD is the CEO of Vyriad and the principal scientist in developing the measles vaccine therapy approach used to treat Stacy. So what happened in the intervening two years?
I had the opportunity to discuss the details directly with Dr. Russell, who continues as a professor at the Mayo Clinic, secunded to Vyriad as CEO. The Mayo Clinic research and clinical team is very strong. They have the capability of manufacturing engineered viruses for phase I and phase II clinical trials, which they did in order to treat more advanced disease myeloma patients with measles virus following the big success with Stacy. Unfortunately, there was limited success with other patients. Measles antibodies in the blood destroy the measles virus before it has a chance to attack the myeloma in the bone marrow. So it was decided to modify the protocol to accept only patients with extremely low—or absent—measles antibodies, earlier relapse (low amount of myeloma), and less immediate prior therapy. Stacy had been off therapy immediately prior to the massive measles injection. This reformulated measles trial has been moving forward slowly.
In the meantime, there has been great progress with rVSV, the engineered alternate virus. There are no blood antibodies to worry about, and laboratory and animal experiments indicate good anti-myeloma activity, as well as safety. A recent paper in Blood shows benefit in acute leukemia combining the rVSV with the PD-LI inhibitor that helps release T cells to attack and enhance the viral killing.
For now, Dr. Russell says the plan is to use the rVSV alone in a phase I-II trial in relapsed/refractory myeloma. The proposed trial is close to final FDA approval and, if all goes well, it can begin in the third quarter of 2016. Dr. Martha Lacy, a colleague of Dr. Russell at the Mayo Clinic, is the Principal Investigator (PI) for this study.
Expectations are high, but, as in so many cases, we will have to be patient to see if this can prove to be a decisive new approach to myeloma therapy. Conceptually, this is a much simpler approach than, for example, individually engineering T cells for each patient using immunotherapy with CAR-T cells. In contrast, a commercial batch of virus can be used to treat many patients, and a manufacturing plant has been established at the Mayo Clinic to do just that.
This is thus a large and brave endeavor by the Mayo team and we can only wish them the greatest of success for myeloma patients everywhere!
From the IMF Newsroom
This initial report of the MMY3004 CASTOR Trial shows the added value of combining daratumumab (Darzalex®) with bortezomib (Velcade®) plus dexamethasone.
2. Comparison of Serum Free Light Chain And Urine Electrophoresis For The Detection Of The Light Chain Component Of Monoclonal Immunoglobulins In Light Chain And Intact Immunoglobulin Multiple Myeloma
This is the first report comparing serum free light chain measurements with urine measurements of light chain excretion.
This small study identifies a method to use GEP data and maintain the prognostic power. (Paywall.)
The toxic exposures at burn pits are a definite concern. This website allows reporting of potential exposures.
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.