We are international
Donate

Measles Virotherapy: Will This Lead to a Cure?

| 6 Comments
DurieBlog_Virotherapy.png
This week I had a chance to talk to Dr. Stephen Russell of the Mayo Clinic about the new measles virotherapy findings and the future of virotherapy for myeloma patients, including a virus that may be an even more potent destroyer of myeloma than the measles virus!

While the news about Stacy Erholtz, a 50-year-old myeloma patient at the Mayo Clinic, may have caught the myeloma community by surprise last week, Dr. Russell, along with Dr. Angela Dispenzieri, have been conducting a trial with engineered measles virus since 2006. In fact, he presented preliminary results at the IMF's International Working Myeloma Group (IMWG) Summit in London in 2011. At that point however, the patients were being treated with lower doses of the measles virus. About three patients per year were entering the study and no responses were seen. 

Then, in May 2013, Stacy was treated with the massive 100 billion dose - equivalent to enough measles virus to vaccinate 10 million people! - and everything changed.

A first patient at the 100-billion-dose level had the intravenous infusion stopped after five minutes because of severe headache. Stacy, the second patient at this dose level, also developed a bad headache, but was able to complete the one-hour infusion. There was a lot of anxiety about possible side reactions. Her temperature spiked to 105°F and she developed shaking chills, which continued over the next two to three days. She also developed surface inflammation at the site of infusion in her left arm. Her blood platelets and white blood cells (lymphocytes) dropped significantly. But dramatically, after 36 hours, the plasmacytoma (myeloma lesion) on Stacy's forehead started to shrink!

A Very Special Patient

Within the first week, her Freelite level dropped. By six weeks, her forehead plasmacytoma had disappeared and the Freelite level plus bone marrow had returned to normal: her marrow was MRD negative according to a flow test. A PET/CT continued to show active myeloma at several sites (in the clavicle, sternum, and T11) but at a much reduced level. By seven months, Stacy's PET/CT was fully negative. As can be imagined, everyone was thrilled.

However, by nine months, her forehead lesion started to grow back. But, there were no other lesions anywhere. This lesion has been treated with local radiation and Stacy is again without evidence of active disease. There will be follow-up testing in June 2014. Thus, a fantastic response, but certainly not a "one-shot cure" yet.

Stacy is a special patient who had myeloma confined to her bones and did not have antibodies against measles in her blood stream. 

How Measles Virotherapy Works Against Myeloma

Of the 31 patients who are part of this measles virotherapy program, about 50% have zero or very low antibody levels. This means that when the engineered measles virus is injected intravenously, it is not immediately destroyed -- as it would be in a patient who had high antibody levels -- and travels to "infect" the myeloma cells. Once in the myeloma cells, the virus "takes over": it divides and divides and divides!! This destroys the myeloma cells (which basically explode), and virus spills into the marrow microenvironment infecting surrounding myeloma cells. 

The virus also activates the local immune system to help "mop up" residual disease in that area. So, this process seems to have worked very well for Stacy and is a tremendous "proof of principle" outcome for her. This type of systemic (whole body) virotherapy can work.

Six patients have now been treated at the massive 100-billion-dose level in two "cohorts" of three each. The second patient in the second cohort also had some response, but to a much lesser degree. This patient also had low measles antibody levels but was rather different in that myeloma was located in muscle tissue outside of the bone marrow.

The toxicities were similar in this second patient, and there was definite uptake of the measles virus into the plasmacytoma tissue documented by nuclear scan. There was also pain at the sites of the plasmacytomas, which seemed promising. But although there was some reduction in Freelite level, by day 45, the level had bounced back up, and the myeloma was clearly progressing again. So quite disappointing compared to Stacy. Of note, this patient has since had an unexpectedly good response therapy using Velcade/Revlimid/dexamethasone.

Next Steps

Treating more patients is the obvious next step. But this is more easily said than done. To produce (manufacture) enough engineered measles virus to treat a patient with the massive dose requires a culture of Hela cells (written about in Rebecca Skloot's bestselling book, "The Immortal Life of Henrietta Lacks") in a 75-liter vat. It takes time to grow up enough virus, then purify, safety check and prepare for intravenous injection. It is estimated that a new larger trial can start by September this year. To treat 100 patients in a trial will require 1,000 to 2,000 liters of cultured cells! For this huge operation a commercial company with a dedicated facility will be used. This is a very expensive project which will cost approximately $50,000 per patient for the massive measles dose. With bulk processing the price will no doubt decrease, and the goal is to achieve a price point of $5,000 per dose.

Dr. Russell openly discusses the magnitude of the project and the commitments which are needed to move this project rapidly forward. The stunning result with Stacy opens many possibilities for further trials.

Other Viruses

Other viruses have been discussed with potential advantages over the engineered measles virus. The measles virus is safe and has been used for many years and thus is very attractive from that standpoint. Another virus, vesicular stomatitis virus (VSV), however, has some attractive features. Since it causes blistering around the mouth, there is no systemic (whole body) antibody response. All patients can be expected to have zero antibodies. In addition, in a model where it is possible to compare, the VSV works faster and is definitely a more potent (in destroying myeloma) versus measles virus. For these reasons, a new protocol with VSV is planned by Dr. Russell and has been submitted to the FDA for review. Feedback is awaited. The clinical lead for this new protocol is Dr. Martha Lacy. Dr. Dispenzieri will continue as the clinical lead for the measles protocol.

Thus, despite many challenges, there is considerable optimism that virotherapy is a dramatic new way forward to treat myeloma using a completely different approach. It may or may not ever be a "one-shot cure" but maybe a "one-two punch" in which follow-up radiation or other therapy can provide a "knock-out" blow. Ideas for further research include ways to increase the number of myeloma cells taking up virus (to 100%, if feasible) and to enhance the local immune "mop-up" process. In addition, as for all novel approaches, combining with/or integrating into other treatments/protocols can undoubtedly improve outcomes.

Dr. Russell will discuss his results at the upcoming IMWG Summit in Milan, Italy. A very lively discussion is expected as the gathered myeloma experts will consider the ramifications of this successful systemic virotherapy breakthrough. Stay tuned!

Dr. Durie sincerely appreciates and reads all comments left here. However, he cannot answer specific medical questions and encourages readers to contact the trained IMF InfoLine staff instead. Specific medical questions posted here will be forwarded to the IMF InfoLine. Questions sent to the InfoLine are answered with input from Dr. Durie and/or other scientific advisors and IMWG members as appropriate, but will not be posted here. To contact the IMF InfoLine, call 800-452-CURE, toll-free in the US and Canada, or send an email to hotline@myeloma.org. InfoLine hours are 9 am to 4 pm PT. Thank you.

6 Comments

This is such encouraging news..I am in my 60's and was diagnosed with multiple myeloma in June, 2012..It was detected inadvertently. I was experiencing pain in my right groin, thinking I might need a hernia repair..Summarizing events after scan not knowing what was wrong and testing done, it was discovered that I had MM and the numbers didn't look good, although, no organs were involved and I was otherwise, in excellent health. My saintly Oncologist, found me while in hospital and several days after discharge was started on Velcade and Dexamethasone...After the first round of chemo, the numbers dropped dramatically...We thought a possible fluke and wanted the test run again..It wasn't a fluke...The numbers kept dropping and am in total remission. It's been two years now...I have had a couple of surgeries since, unrelated to the myeloma and recovered quickly...I am a nurse and although not working at this time, I get calls from acquaintances that either have cancer or think they might have myeloma to ask me what to do...I am so happy to hear of other treatments that are successful..Thank you for sharing..

Dr. Durie,

Hello, I appreciate your insight into these exciting times with virotherapy. My search continues, and I am most hopeful. My follow up yesterday 5/21 was very encouraging, including my discussion with Dr. Jan Morab, who after soliciting his insight on virotherapy, brought to light his own research. He co-authored "Selective Purging of human multiple myeloma cells from Autologous stem cell transplant grafts using oncolytic myxoma virus" which by his indication Phase 1 is very near. Yes, indeed these are exciting times and a cure will be possible.

All the best,

David Vermillion

Dr. Durie,

Thank you so much for the complete review of the virotherapy breakthrough. Friends have been sending me notes and links but the information has been incomplete, at least until I found the Mayo site. Your review is very much appreciated.

Until Myeloma retired me I was in the soap manufacturing business. Soap making begins in an 8,000 gallon stainless steel tank. Wish I could make one available to grow measles virus.

We've met at two Myeloma patient seminars. I am grateful for the commitment you and Suzie have made to Myelomics.

Michael Lapides

ALRIGHT! Glad to hear our immune systems get to work on this! I am still going up and down with the Thalidomide family of drugs--How do we find out about signing up for a trial on this? Do we need to save up $50K so we can participate???

Thanks so much for clarifying the information about the measles virus. I hope something is found that works while I'm well enough to get it.I really appreciate your blog and Myeloma Minute talks.:-)

Dr. Durie,

I am Kerim Ustunel's daughter, a multiple myeloma patient diagnosed in August 2011. He told me you two met in Istanbul-- his doctor is Dr. Burhan Ferhanoglu and that you even examined him both in Istanbul and Rome back when he was first diagnosed. As time flies, he went through lots of things - his disease turned into secondary plasma cell leukemia last summer and he miraculously overcame a severe pneumonia. After recovery from the pneumonia, Dr. Ferhanoglu had started the VDT-PACE treatment for two consecutive cycles and at the end of the second cycle, which was back in September 2013, we travelled to Rochester, Minnesota where we currently are now.. Under the decisions and guidance of our doctors at the Mayo Clinic, Dr. Rajkumar and Dr. Shaji Kumar, my father underwent an allogeneic bone marrow transplantation from an unrelated donor (9/10 match) in November 2013. The 100 day period was tough, but thanks God he is OK now, presenting some little GVHD signs (skin rash and mouth/eye dryness).. His Freelite levels started to rise a bit couple of weeks ago, so our doctors made him take Velcade once a week for 6 times in total. Dr. Kumar foresees to apply a T-cell infusion (of the donor) but we are in the phase of patience right now, as my father developed some GVHD signs that might hopefully decrease the Freelites to a total cure..

I just wanted you to have an idea of the current situation and my question is if my father would be a candidate for these developing virotherapies, as he underwent a bone marrow transplantation..

Thank you very much for your time and sharing these exciting news!

All the best,
Belis Ustunel

Leave a comment

To subscribe to this blog, enter your email address below: