A segment on last Sunday’s edition of the CBS news show 60 Minutes illustrated how the injection of poliovirus into brain tumors can be dramatically effective. Three years after receiving the poliovirus treatment at the Preston Robert Tisch Brain Tumor Center at Duke University in North Carolina, a young woman featured in the program is entirely well and has just graduated from nursing school. There are no cancer cells left in the area of the glioblastoma, a notoriously aggressive brain cancer that is very resistant to treatments. Is she cured? She and her doctors would certainly like to think so!
What do these results mean for myeloma patients? Firstly, unfortunately, the poliovirus is much too toxic and dangerous to give in to the blood circulation to attack myeloma in the bone marrow. This virus cannot be used for bone marrow cancers. But, as I have reported, other viruses that have been carefully selected and engineered can be used to treat myeloma. This is called “systemic virotherapy” as compared to local injection of the virus into a brain or other localized tumor.
We reported the early exciting results using engineered measles virus—the form used for measles vaccination—adapted to attack myeloma. As with the poliovirus, the dose of the measles virus had been increased over time to assess for safety first, but also to see if responses were occurring. This is a phase I study in which typically three patients are treated at each dose level before moving to the next higher dose monitoring for safety. It can be difficult to balance the value of responses with the concerns about safety. As was shown on the 60 Minutes report on the poliovirus trial, the lower dose worked really well three years ago for the young woman who is now a nurse. Clearly very effective. However, there were concerns because the virus triggered a major immune response against cancer with brain swelling and inflammation as the cancer was being wiped out. Later patients receiving higher doses of poliovirus had too much swelling and inflammation and had critical problems.
Thus, due caution is required with these types of early trials with paradigm-shifting new treatments.
So do these viruses work against cancer? And, if so, what is the best dose? In the case of the measles virotherapy research, a phase II study was started at the Mayo Clinic in the fall of 2014, and Dr. Martha Lacy from the Mayo Clinic mentioned at the recent San Francisco IMF Patient & Family Seminar that about a dozen or so patients have been treated so far. Results have not been released yet. However, we do know that it was difficult to find patients who did not have antibodies against the measles vaccine since most of us have been well vaccinated. The presence of the measles antibodies block the virus and react with the virus to cause high fever (as occurred in the early patients) and reactions with headaches and other problems. Everyone is keen to learn how things are going with the measles virotherapy trial with Dr. Stephen Russell and the team at the Mayo Clinic.
Meanwhile, the Mayo team is preparing to start a trial with another virus that can be given safely as systemic virotherapy to treat myeloma. The vesicular stomatitis virus (VSV) is a type of virus that can cause blistering of the lips, like herpes. The body does not have antibodies against VSV, so all myeloma patients can be eligible for treatment. Studies in the laboratory have indicated that this is a very effective virus for treatment—probably better than measles—so, very promising. If the awaited FDA approval comes through, trials will start later this year.
What does all this mean for myeloma patients? The virus treatment approach can definitely be dramatically effective. In one of Dr. Russell’s early reports, he discussed this as a possible “one-shot cure” approach because even patients with advanced disease could have amazing benefit with just one IV shot! Pretty amazing, but still too early to know.
The potential here is enormous. The researchers working on this and the patients involved in trials are true pioneers. This is a new frontier with a cure on the horizon. Keep your binoculars handy to monitor progress!
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®.
