Manmeet Ahluwalia, MD, a medical oncologist and associate director of the brain tumor at the Oncology Center at the Cleveland Clinic, talks about a new vaccine that can fight glioblastoma.
What’s a glioblastoma?
MANMEET AHLUWALIA: Glioblastoma is not only the most common but also the most aggressive brain tumor, which starts in the brain and generally stays in the brain. It’s is a type of a primary brain tumor.
It’s very hard, right, to treat because what I understand is it kind of has like tentacles.
MANMEET AHLUWALIA: Glioblastoma is extremely difficult to treat because they spread as spider webs or tentacles and hence even with surgery, we can never remove it completely. We use radiation and chemotherapy to treat these patients. Typically the outcomes are fairly dismal, despite all the advances we’ve made in these modalities.
What’s the five year survival rate?
MANMEET AHLUWALIA: Unfortunately despite all the advancements, the average patients survive around 15 to 18 months and the five year survival for most patients on trials is ten percent. With standard treatment, it’s around 5 percent.
And you’ve started a new trial?
MANMEET AHLUWALIA: Yes, we are excited about this vaccine trial that combines a vaccine with an immunotherapy called pembrolizumab in recurrent glioblastoma. We had previously collaborated with Roswell Park Cancer Institute, Dana Farber Cancer Center as well as Mass General and Beth Israel to treat 63 patients with the vaccine on a newly diagnosed Glioblastoma trial and the patients did much better than what we would expect from standard of care.
What is this vaccine?
MANMEET AHLUWALIA: This is a peptide based vaccine that targets survivin. Survivin is a protein that is expressed by cancer cells and is not present in normal cells. When we give this vaccine to the patients, it basically boosts their immune system to mount a response against the survivin which is there in the cancer cells, and this immune system then helps fight the cancer.
Seems like it’s all about immunotherapy right now.
MANMEET AHLUWALIA: As we know in the last five to 10 years, the cancer treatments have changed dramatically because of immunotherapy. Patients who have stage 4 lung cancer where, on an average, they would survive twelve to 15 months, almost 25,30 percent of them with stage four lung cancer are now living five years out. This number used to be close to five percent. That’s where we are with Glioblastoma . Our hope is that with immunotherapy we can make advances in this very difficult to treat disease.
How does this vaccine work? How do you give it? How long do they get it?
MANMEET AHLUWALIA: The vaccine is given in the shot. We give the shot every two weeks times for to begin with. This is called induction phase. Once the patient gets the induction, then they get a vaccine roughly every three months in maintenance as long as they are getting benefit. The vaccine is well tolerated, and we have not seen any serious side effects with the vaccine in previous studies.
Now, would this come after operation and chemo and radiation?
MANMEET AHLUWALIA: The vaccine is given after patients have undergone a surgery, and then they have completed six weeks of radiation and chemotherapy. This is what we consider as the backbone of treatment for Glioblastoma patients. The vaccine is an adjunct to what they would get as their standard of care.
Is this for first time glioblastoma treatment? Or someone who’s had a reoccurring maybe once or twice, can you try this?
MANMEET AHLUWALIA: The good news is that the trial that we did was in newly diagnosed setting. It was for patients who had just been diagnosed, had undergone surgery followed by radiation and chemotherapy and then they received vaccine and chemotherapy. But we have our upcoming trial, which is going to open next month. We are combining the vaccine with immunotherapy called pembrolizumab, which has been FDA approved in a number of other cancers. So, we’re going to combine two strategies of immunotherapy to boost the immune system even more. That trial will be open for patients whose Glioblastoma has grown after initial surgery, radiation and chemotherapy.
Are you still looking for patients?
MANMEET AHLUWALIA: Yes, we are. The trial will open next month and we will have at least 40 open slots.
With the trial that you did, it says nearly 90 percent of the patients, 97 percent, did not experience tumor growth?
MANMEET AHLUWALIA: The outcomes of Glioblastoma are typically dismal. Despite our best treatments, patients on an average live 15 to 18 months. What we found out on this vaccine was when we treated those patients the average survival were over two years. Twenty-six months from the time they got the vaccine, half of the patients were alive. But what was also very interesting on this trial was that typically glioblastoma patients outcomes are determined by MGMT. Patients who are MGMT methylated typically do well with chemotherapy and radiation. Unfortunately, those who are unmethylated don’t do well. Their average survival is close to a year. But patients who got this vaccine in both methylated and unmethylated groups did well. So, we might be able to make a difference in two thirds of our patients who are unmethylated who do not get good benefit with chemotherapy and radiation. This vaccine may help them more, which is very interesting and promising for us.
It has to be very exciting for you because a lot of times, you know, you don’t get to come with good news.
MANMEET AHLUWALIA: Definitely, I mean, Glioblastoma is a tumor where we need to make inroads. A lot of cancer diagnosis and outcomes have improved in the last 10, 20 years. There are some cancers which still need a lot of work to be done and Glioblastoma remains one of them. This vaccine, certainly due to the fact that this does not have any serious side effects, we could easily add it to the other therapies that these patients get. It’s very promising news for us, but more importantly for the patients.
Now why does it seem like maybe in the past five years, seven years I just hear so much more about glioblastoma? Is it more? Is it happening more?
MANMEET AHLUWALIA: I think A) there is greater awareness as our diagnosis have improved, and we are seeing more patients that we have seen in the past. There were some worries about cell phone use and increasing Glioblastoma. So far, the studies have been inconclusive. However, we are seeing a greater number of diagnosis of Glioblastoma . We are also seeing more and more of elderly patients. Initially like 10, 20 years back, our median age of diagnosis was less. Now, the median age of diagnosis is around 65 years of age. As people live longer, cancer becomes more common. So, we are also seeing a greater incidence of Glioblastoma these days.
Anything I’m missing? Do you have to come here to be in the trial?
MANMEET AHLUWALIA: Yes the trial will be open at Cleveland Clinic and people will need to travel to Cleveland Clinic to get the treatment. But in our previous trials we had several out of town and out of state patients.
END OF INTERVIEW
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