Latest / EHA Unplugged / Hematology Portraits: Prof Kostas Stamatopoulos

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Hematology Portraits: Prof Kostas Stamatopoulos · EHA Unplugged

• 0:07
  Greetings and welcome to EHA Unplugged, the official podcast
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  channel of the European Hematology Association EHA.
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  Hello. So I am Isabel Olivera, a
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  medical writer at the European Hematology Association, and I
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  have here with me today Costas Stamatopoulos.
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  He's a professor of hematology and he's the research director
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  of the Institute of Applied Biosenses at their search in
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  Greece. Hello, Elizabeth.
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  Thank you for being us here today.
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  We are here because we are interested in learning more
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  about your career. You are trained as a medical
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  doctor and as a researcher, and we wanted to understand first
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  what place these two positions have played in your career.
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  They were always linked and I could not distinguish one from
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  the other. In the end, I think that a
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  reason why I became a hematologist is that I realized
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  that there were so many opportunities for doing research
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  and the particularly I was very interested since the very
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  beginning into molecular biology and hematology offered a great
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  opportunity for that. Do you work with patients today?
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  I still work with patients today, but in a different
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  function. So since I moved from the
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  hospital to the Research Institute that happened 12 years
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  ago, things were different. So it's different things that
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  you can do from a Research Institute.
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  And the thing that I decided to try at the time was doing
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  involve to engage scientists from other disciplines, in
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  particular health psychologists and and data scientists to work
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  together towards supporting patients in care for us.
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  This is a major priority. How can you ensure that patients
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  get what they deserve through being better informed and
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  empowered in managing the disease?
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  It's for me, it was an entirely new path, but it was my way of
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  doing things that could be, let's call it directly relevant
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  for patients because what we do in research should always be
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  addressed at should always be addressing patient needs.
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  But it can take time between what you're doing today and what
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  will be impactful years later. You have mentioned why you got
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  interested in hematology, but could you also explain why you
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  became focused on CLL? Oh, it's, it was a choice of, I
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  will say common sense and necessity.
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  I don't think I'm planning things in life ever.
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  And even hematology was not planned.
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  It just came about. I was always interested in
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  molecular biology, as I told you I I liked understanding how
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  things work. And it happened that my first
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  mentor, Dimitris Lucopoulos, happened to be a hematologist.
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  So as a medical student and I was exposed to things like DNA
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  and recombinant DNA techniques. That was the 80s through his
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  lessons. So while I was serving as a what
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  we call doctor in the in a small province, in a small village,
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  while doing that, I was translating something I also
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  like doing. I was translating books in
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  molecular biology and biochemist from English to Greek.
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  And then there were some molecular biology terms that I
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  couldn't translate. So I went to him and he said we
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  have a molecular biology lab, would you want to join?
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  And I did. So I knew that cancer was more
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  interesting to me than other diseases.
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  So when I decided to stay, I started in lymphoid cancer in
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  particular, I was very fascinated by the complex
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  processes through which lymphocytes, they can become
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  cancers and giving lives to leukaemias and lymphomas,
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  including CLL. So I was very intrigued by the
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  mechanisms of lymphocytes, how they can ensure diversity, how
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  they can ensure that we can defend ourselves.
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  And I happen to have the immense lack of collaborating with a
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  major pathology lab in Athens. So all of a sudden I had access
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  to a huge collection of relevant material.
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  And my first area, the first thing that interested me a lot
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  was lymphomas, in particular follicular lymphoma.
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  CLL started being interesting for me almost 30 years ago and
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  then over time I understood that it was think that would be, you
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  know, that we still have many, many unexplored areas.
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  Then we moved with my wife from Athens, where we were both
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  working to Thessaloniki and I said that it was by chance
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  because we had never planned going there and that CLL was a
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  choice of necessity in the end for the very simple reason that
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  in Thessaloniki I wouldn't have access to such valuable, well
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  characterized, well processed material as in Athens.
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  Now CLL is a different, a bird of a different feather amongst
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  lymphomas in that you can get the material that you need in
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  order to run your studies easily from a simple blood drawing.
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  So it would be far easier for me to get the material that I
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  needed, which is why 25 years ago I shifted the focus of my
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  work from, let's call them lymphomas predominantly located
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  in lymph nodes, nodal lymphomas, to lymphomas with a leukemic
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  presentation like CLL 20. Five years ago, the B cell
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  receptor was shown to be central to the pathogenesis CLL.
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  How did this discovery influential career?
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  You are absolutely right by saying that it was 25 years ago,
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  but do you know when this information was incorporated in
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  recommendations about how to manage patients?
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  It was only 2018. So it took 19 years before this
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  knowledge became known to implementing it in routine.
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  And it took almost 13 years before we understood why the
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  immunoglobulin genes and the immunoglobulins in particular
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  can be critical for the for understanding this disease to
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  developing drugs that target how the immunoglobulin functions.
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  I think that's a very good example for what I was saying
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  before, that it can take years between a discovery and a change
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  in how we manage and practice patients.
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  But to your question, how it affected my work, even before
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  concentrating, I would say almost 100% on CLL.
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  My main research was immunoglobulin genes.
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  So molecular analysis of the immunoglobulins.
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  Now I I was doing that in follicular lymphoma, I was doing
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  that in diffuse large basal lymphoma.
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  I had started doing that in CLM, but then seeing the two Seminole
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  publications by Nick Curazi and Freda Stephenson and their
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  groups made me invest more. So in the end, it assisted in,
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  you know, concentrating my attention on one particular area
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  in one particular direction. Was it at the time that you
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  showed that there is an improved survival for CLA patients when
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  they have a mutated immunoglobulin gene?
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  Was Freda and Nick who first reported that and then we
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  contributed to this knowledge. Our contribution, if I may use
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  the term to the field, was to delving deeper into a phenomenon
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  that was first described in CLL. It's called stereotypic of the B
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  cell receptor, stereotypic of the immunoglobulin.
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  And in a minute I'll try to explain what this is about.
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  South CLL is a disease of B lymphocytes.
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  B lymphocytes are a critical part of our adaptive immune
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  system. The adoptive immune system has
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  to recognize an immense number of elements, particularly
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  pathogens. Now pathogens may have different
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  structures, structures called called antigens that are
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  recognized by lymphocytes and the recognition is mediated via
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  the immunoglobulin, the B cell receptor.
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  Now the repertoire of antigens is immense and for us to be able
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  to respond to that, we need an equally immense repertoire of B
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  cell receptors. There are estimates that we can
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  have up to trillions of different B cell receptors,
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  meaning trillions of different B lymphocytes.
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  Now This is why the immunoglobulin is kind of a
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  molecular signature for each B lymphocyte.
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  Let's move now to CLL. Whether CLL?
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  CLL is a clone of B lymphocytes, In other words, a population of
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  cells from a common ancestry ancestral cell.
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  The common ancestral cell carries a particular
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  immunoglobulin, so all its progeny will carry the same
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  immunoglobulin. So if you look at different
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  patients, you are looking at different clones.
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  The immune system is diverse, the immunoglobulins are diverse.
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  So I told you that we can have up to a trillion if not more of
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  different immunoglobulins. So in principle, if things were
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  happening by chance, you will need to study one trillion
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  patients with CLL. There are not one trillion
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  patients obviously to find 2 with identical immunoglobulins
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  and yet we and others have managed to identify individuals
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  with identical or very similar immunoglobulins in small groups
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  of 3400 patients. That was 2025 years ago.
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  So just consider one in a trillion versus a few in a few
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  hundreds. It cannot be by chance.
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  So it means that it is likely driven by something.
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  Now studies that we did over the years focused on this phenomenon
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  stereotypic. And what makes me very happy
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  today is that thanks to a collaborative effort of
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  different institutions from all over the world, we managed to
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  convey the message that this stereotypy occurs on at an
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  unprecedented scale in CLL. And that if you have different
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  patients expressing the same or similar highly similar
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  immunoglobulin, you can consider them as a subset.
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  Some of these subsets follow have a very different biology,
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  unique biology different from other subsets, and this
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  information regarding subsets assists in running dedicated
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  research that helps identify what is happening in particular
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  groups of patients in other way. In other words, it's a powerful
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  tool for overcoming the very pronounced heterogeneity of CLL.
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  So each one of these subsets will be susceptible to different
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  drugs. In principle, yes, but in
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  reality we are. We should be grateful as
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  healthcare professionals that we have so very effective options
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  these days. I mean things change
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  dramatically compared to 10 years ago even there has been a
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  revolution in how we manage CLL. Still, CLL remains incurable in
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  spite of all the progress. So we do have drugs and in fact
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  one major class of drugs targets BDK inhibitors.
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  They target the B cell receptor and the signaling pathway
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  initiated through triggering of the B cell receptor.
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  But should we accept or expect that these drugs would work
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  equally well in every patient? The answer is not really, though
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  admittedly they are excellent. They are very effective without
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  curing the disease. So a lot remains to be done
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  until we reach the ultimate goal, which is curing patients.
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  And we believe that through focusing on this subsets, you
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  can identify mechanisms that are pathogenetically important and
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  that can assist in directed research that can identify new
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  targets for eventually curing the disease.
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  Are you also using this substance for risk
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  certification? Yes, we are doing it for that
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  and it's very reassuring that the wider community has endorsed
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  this principle, at least for two of these substance.
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  They are both quite aggressive and they are called subset #2
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  and subset #8. And colleagues in different
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  places in Europe and the US and other parts of the world are
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  including this information regarding subset 2, in
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  particular for stratifying patients in clinical trials.
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  So this is a major development. Just consider that until 20/18
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  it was not even recommended as mandatory to test for
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  immunoglobulin genes. So we have indeed made great
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  strides in less than six years. Which are the major findings
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  that you made during your career that had or are having a
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  clinical impact? I think that, I mean, I should
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  probably not be the person to reply this because I would
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  somehow claim that what I did was impactful and I cannot be
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  the best judge of myself. But I would say that investing
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  in and then for investing in immunogenetics and emphasizing
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  on the need to consider the immunoglobulin, the B cell
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  receptor as key to understanding and treating CLL is what I
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  consider as the major thing I did.
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  I hope it has contributed to an extent into improving how we
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  manage this disease. And I leave it at.
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  That so we know that you're also very involved in passion
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  empowerment. Why is this important for you
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  and what have you been doing about this?
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  Patients are citizens. We are citizens.
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  We are potentially patients. So the change from being healthy
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  to becoming sick is so dramatic it can happen to everyone.
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  And the top turns everything, particularly in hematology,
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  experiencing how lives can be destroyed even and not only the
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  patients lives, but also the lives of their family, their
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  friends, is what motivated me to try and somehow ensure that we
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  move from the current model of healthcare delivery, which is so
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  horribly focused on the physician has got to a different
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  model that would be far more democratic, egalitarian and
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  participatory. But for that to happen, you need
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  to do a lot of things, including directly and supporting
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  patients, and then finding ways to ensure that physicians
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  endorse the concept and improve the way that we communicate
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  things to our patients. It's not easy.
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  It's not at all easy, but I think that unless we do it, we
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  run a very big risk of disconnect with the way society
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  moves. Because just consider having
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  patients who will be receiving a diagnosis of CLL or for that
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  matter any disease, and then they are left on their own to
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  come to terms with the complexities of their condition,
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  the practical difficulties, the anxieties, and also run the risk
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  of being misinformed or disinformed.
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  It's not something we as society and we as physicians should
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  accept, do. You think there is a role then
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  for the patient on the decision of how they are?
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  Treated absolutely, absolutely. Patients, in the end, is
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  patients who should take the ultimate decision, but only
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  after they do it in a shared way with the healthcare team.
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  Is it happening today? Not to an extended shoot.
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  So when we invited you for this interview, you said that your
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  career was not worthy of being considered inspirational after
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  this quick overview of how things have gone, I know it's
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  not all you who have done this, but it's collectively how do you
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  see your career now? That's a difficult one because I
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  my career today is in simple words, I'm fed up of the classic
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  way of doing things. I'm very much into education and
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  training as a transformative process whereby we communicate,
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  and for that to happen, I think that we need to experiment more,
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  find new ways of communicating about concepts rather than
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  facts. So my career, this stage is
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  about ensuring that things become more democratic and more
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  participatory. This requires a lot also a lot
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  of trial and error for me, and it also requires finding the
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  right balance between what I'm hoping and what in the end may
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  be achieved. It's not easy, but I find it
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  quite inspiring. So educating, educating people
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  and particularly making sure that young people find their own
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  way of doing things through being exposed to different
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  perception, to different perspectives is very important
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  to me also in the context of AJ. So thank you very much, Costas,
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  for generously sharing your experience with us and thank you
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  very much to everyone for listening.
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  Thank you very much, Isabel, for this discussion.