So, Dr. Scholz, we've picked up some questions regarding immunotherapy from
our YouTube comments section, and I think we should start off with what
is immunotherapy in prostate cancer, and how does it work?
Well, the only FDA approved immunotherapy is a vaccine-type therapy called Provenge
that involves taking immune cells out of your bloodstream kind of in a dialysis type procedure,
and then those cells are fed pieces of prostate cancer—they actually use a molecule
called prostatic acid phosphatase—and then they activate the cells with leukine or GM-CSF—all
this is done outside the body in a vat—and then the cells are multiplied, and then put in a bag
shipped back to the oncologist who ordered the Provenge for the patient and then it's infused
back into the patient. So, these activated immune cells then sniff out prostate cancer and turn on
that individual's immune system to fight the prostate cancer better; kind of the way
a vaccine would, I suppose. That's the only FDA-approved immune therapy. There are other
for prostate cancer there are—other immune therapies—that are being studied.
Are there any side effects to Provenge?
The only real side effect that I typically see is some fever,
chills in a minority of patients during the day of the infusion. The infusions are given
every two weeks for a total of three infusions, but most people don't have any side effects. Some
people have said they maybe feel a little tired on the day of the infusion, but it's very minor.
So, Provenge has been approved for almost, I think, it's nearing 10 years,
and you know, you've treated many many patients with Provenge over the years,
so how have you seen this effect on their immune system help fight prostate cancer?
Well, that's the funny thing about the immune system is it's working in all of us right now.
We all have a bunch of bugs in our intestine that if they get out of the intestine could kill us.
E. coli, if it gets into the bloodstream, is highly lethal,
but our immune system somehow quietly keeps all this stuff in check and the way that Provenge
works to inhibit prostate cancer growth actually happens very silently. We don't measure it with
declines in PSA like we do with chemotherapy or hormonal therapy. The way it was established as an
effective therapy was in double-blind trials where half of the people got the treatment, half didn't,
and the ones who were treated lived longer, and that trial has been repeated
and shown to have a valid improvement in survival. So, the assumption is it was the Provenge that
did it; that was the only thing different between the two groups of patients. Yeah,
so measuring what happens in each individual patient is not clear just like measuring the
impact of a vaccine in any individual patient is not clear who the vaccine helped; you just know
from large population studies that vaccinated people do better than unvaccinated people.
So, in that sense then, do you believe in giving Provenge to active surveillance patients?
Can a patient take a Provenge at any given stage or what is the FDA approval for it?
So, it's a very expensive treatment and therefore it's usually reserved for people
that have become resistant to hormone therapy, who have a
metastasis of cancer outside the prostate. It has been studied in earlier stage disease and
I'm not sure what the impact was. That, I believe, is still pending,
and I'm going to be interested to see how much of an impact it has in earlier-stage disease.
It is clear from the studies that have been done that people who have Provenge who are hormone
resistant do better when they start with a lower PSA in terms of improvement in survival. That's
kind of logical that the immune system will have more leverage in someone who's not battling such
massive amounts of cancer but has a more manageable amount of cancer in their body.
One thing we've heard a lot of news about is Keytruda and I know it's not
FDA-approved for prostate cancer at this time but they have— the company
Merck—has allowed you to use it for compassionate care use, and other
oncologists. So, can you explain how Keytruda works and what the side effect profile is?
Well, yeah Keytruda is FDA approved to treat lung cancer, bladder cancer, and apparently a
dozen other cancers. It's an infusion given every three weeks. Classically, it's been described as
a medicine that takes the brakes off the immune system. Why are there any brakes for the immune
system? Because an immune system that runs out of control can result in rheumatoid arthritis,
lupus, multiple sclerosis, all kinds of nasty things of an uncontrolled immune system. The
side effects that you inquired about are those sorts of problems where people get rashes or
inflammation of their lungs or their GI tract, diarrhea, asthma—these sorts of things, and
just about any area of the body can potentially suffer as a result of an overactive immune system.
So that, of course, weighs with the fact that a more active immune system can fight cancer better,
and that is being studied in prostate cancer in large phase III trials. We've done some
phase II trials; that means we just give it to a bunch of people and see what happens,
and we've seen PSA declines, PSA stabilization. When the topic of Keytruda comes up, I always
mention the fact that Joanne Weidhaas at UCLA has developed an assay to figure out who's
likely to get toxicity from Keytruda, which is very handy. If you're treating a healthy
person with a medicine that could make you very sick, you'd really like to know
how likely it is to cause toxicity. So, we've been utilizing her services and by selecting
people who are at low risk for toxicity we're thankfully not seeing much of any toxicity.
So how many patients would you say you've treated so far?
Well over 100. I don't know precisely how many.
And what type of percentage success have you seen with PSA stabilization and cancer-free survival?
So, we try to pick patients with lower PSAs and smaller amounts of cancer. If you select patients
that have widespread cancer with very high PSAs that are rising quickly, I don't see a whole lot
of utility in those groups. In patients with lower PSAs and smaller amounts of cancer, I'd say about
half of the patients get either stabilization of the PSA rise or even a reversal in their PSA.
I know we're still waiting for the trials and everything to come out,
but when do you think this will get approved for prostate cancer patients by FDA standards?
Well, of course, we don't even know that it will be. The phase III trials—this is where
the half the group gets the treatment, the other half doesn't, and then they
compare their outcomes over time, usually a survival endpoint—are still, you know, still
pending. When will those trials be completed? I don't know; maybe in the next year or two.
If somebody's interested in taking Keytruda,
is it possible that any oncologist can get it for them for compassionate care use?
Absolutely, yeah. Merck has been very generous—the manufacturer Merck—has
been providing the the product to us free of charge and and
these hundred plus patients that we've treated were all on a compassionate use basis.
So, another immune therapy that we keep hearing in clinical trials is CAR T-cell therapies,
and I know that Tanya Dorff with City of Hope has been doing all sorts of trials in these,
but can you explain what the future of immunotherapy can look like with CAR T-cell?
I don't know what the future is going to look like. All I know is we've had
a handful of patients that have been treated with it and we've had a couple patients with
dramatic reversals in their PSA. It clearly was beneficial. These treatments do come at a price
because the patients are treated in a hospital setting and sometimes they have rather notable
side effects with drops in blood pressure and this sort of thing. I'm probably not the most
sophisticated person to give you an answer in terms of all the details of CAR T-cells, but
they've been approved for things like lymphoma, and have made a big difference in that setting.
Whether they're going to pan out in prostate cancer, I think, is still an unanswered question.
So, I think in the prostate world we also hear about leukine as an immunotherapy. So,
can you explain what that is and also what the side effect profile is?
So leukine was originally approved to help people with
impaired immune systems right after chemotherapy. Chemotherapy causes a transient drop in your white
blood cell count which is a measure of your immune system, and subsequently it was discovered by Eric
Small, up at UCSF, that the GM-CSF or leukine, as it's called, can inhibit prostate cancer growth,
and he studied patients who had rising PSAs after surgery and noticed that in about 20 percent of
the patients that were given leukine injections, it's like an insulin shot, subcutaneously
for two weeks straight, then a holiday of two weeks, and then two weeks straight,
that about 20 percent of the patients were treated in that fashion had stabilization of their PSA
out to five years, and the side effects as you were inquiring about really aren't that
bad. I mean sometimes people get a little bit acid stomach with it, you know, some rarely,
other things like rash or whatnot, but most of the time there are not many side effects at all.
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