PracticeUpdate: Haematology & Oncology | Vol 1. No 4. 2016

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EDITORIAL
Managing Editor
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Consultant Haematologist,
Medical Oncologist
SALES
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EXPERT OPINION
Future of immunotherapy and biomarkers in
prostate cancer
Interview with
Gautam Jha, MD
Dr Jha, Assistant Professor, University of Minnesota Medical Health in the US speaks
with PracticeUpdate’s Farzanna Haffizulla, MD, FACP, FAMWA, on enhancing the
immunotherapy response.
Dr Haffizulla: What about the future for immunotherapy?
What’s on the horizon? What biomarkers might we be
looking at, or other prognostic or predictive markers in
immunotherapy?
Dr Jha: One of the biggest drawbacks with immunotherapy,
in general, is that there have not been good biomarkers. For
example, at least with the PD-1 line of therapy, we look for
PD-1 expression and, again, we know that it is dynamic, and
it does not always correlate with response. Unfortunately,
PD-1 hasn’t worked as well in prostate cancer as it has in
many other cancer types. However, I think there is a big
promise with immunotherapy; we have sipuleucel-T, which
is already approved, and PROSTVAC, which is in later stages
of development.
Combining this with our checkpoint inhibitors like either
ipilimumab or PD-1 inhibitors or, in fact, a new inhibitor.
I have my own investigator-initiated trial with indoximod,
which is an IDO inhibitor, which suppresses the inhibitory
Tregs and would allow a much more enhanced response to
sipuleucel-T. Those combined with other cytokines like IL-7
or IL-15 would be quite promising. So, this would make this
modest response from sipuleucel-T or PROSTVAC into a
much more enhanced response, which might last for a long
period of benefit.
Dr Haffizulla: Let’s talk about the role of immunotherapy in
prostate cancer. Where we were, where we are, and where
we’re going. We mentioned sipuleucel-T. Let’s talk some
more about that particular vaccine and where we’ve come
from that point.
Dr Jha: Sipuleucel-T was the first landmark vaccine in that
it was the first to get approved and was the first step in the
right direction. Consistently, trial after trial, it was shown
that it could improve survival, offering us a survival advantage
of over 4 months, which was unheard of at that time. The
important thing is that it is such a well-tolerated therapy. The
only drug that worked before sipuleucel-T was docetaxel,
which has substantial toxicity, as you know, and the survival
advantage gained with that was barely 3 months or so.
Dr Haffizulla: You want to minimise the toxicity and maxim-
ise the efficacy, and, of course, you’re looking at cost, and
you’re looking at the individual patient, and if this suits his
particular clinical scenario.
Dr Jha: Yes; there has to be an individualised approach, and it’s
clear that vaccine therapy, especially sipuleucel-T, is not for
everyone. It has been approved and tested in only a very spe-
cific set of patients, patients who were castration-resistant
but had either minimal symptomatic disease or were com-
pletely asymptomatic. We’re talking about patients who were
in extremely good health, had no visible disease, and were
not taking an opiate for pain; so, essentially, these were the
guys who had an anticipated survival of least a year or more.
This is not a therapy that you would do at the end of the road,
or in patients who have progressed on lines and lines and
lines of therapy or someone who has a huge disease burden;
you would not be benefiting the patient. In fact, you might
be harming him by delaying more effective therapy.
Dr Haffizulla: It makes me think about using these vaccines
in prevention for patients who may have a very strong fam-
ily history or may have other risk factors. What are your
thoughts on using it in prevention?
Dr Jha: It is quite interesting that you bring it up. Some call
it a vaccine. Essentially, a vaccine is something that would
enhance our immune response to fight the disease, but this
one does not prevent the occurrence of disease. It would
be great if we had something which could do that, and if it
would be effective.
The cost of this thing is so prohibitive that we have to select
the right patients; the population who is going to benefit
from this therapy. And this is a tremendous thing because
it works and it is very well tolerated.
Dr Haffizulla: Yes, because the way these vaccines are cre-
ated, as you mentioned, are from the actual tumour itself,
from the patients themselves, or from their peripheral blood
mononuclear cells.
Dr Jha: Yes. This is essentially using the antigen-presenting
cells of the patient, and the dendritic cells, which are col-
lected and are sensitised outside the patient’s body to es-
sentially one of the proteins expressed on the cancer cells,
prostatic acid phosphatase.
This is not a tumour-based vaccine. There are some tumour-
based vaccines, but none of them are far enough in develop-
ment for prostate cancer. There are some being tested, but
that arena is much more advanced in, say, kidney cancer
melanoma. So, some tumour-based vaccines are in develop-
ment, but not as much for the prostate.
Dr Haffizulla: Let’s talk some more about the future of im-
munotherapy. We just discussed sipuleucel-T and it being an
effective adjunct to the therapeutic landscape already. What
are your thoughts on what might be happening in the future?
Dr Jha: With our improved understanding of immunotherapy,
I feel things are changing, and we will start seeing more
and more results. I feel that we could combine one of those
checkpoint inhibitors, and all of the cytokines to enhance or
augment the current immunotherapy. Things like sipuleucel-T
or PROSTVAC, and checkpoint inhibitors like CTLA-4 or
like PD-1. As I mentioned, I am working on a trial using an
IDO inhibitor, which is an enzyme but inhibits or is quite
immunosuppressive. In other words, an inhibition that will
enhance or augment the response to immunotherapy. This
would be quite compelling.
Dr Haffizulla: So, really stepping back from the picture and
looking at ways that we can have a vertical blockade and a
horizontal blockade, more synergism really in the therapeutic
paradigm.
Dr Jha: Synergism, yes. Exactly.
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Scan this QR
code, to watch
this interview
with Dr Jha.
PROSTATE
VOL. 1 • No. 4 • 2016
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