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Hematology Portraits: prof. Martin Dreyling · EHA Unplugged

• 0:03
  Greetings and welcome to EHA Unplug, the official podcast
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  channel of the European Hematology Association, EHA.
• 0:10
  Hello. I am Isabella Rivera, a medical
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  writer for EHA. In this series, we are exploring
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  the world of hematology through conversations with leading
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  experts in the field. Today we have the privilege of
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  speaking with Professor Martin Reilling, a professor of
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  medicine and head of the Lymphoma program at Ludwig
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  Maximilian Universite LMU in Munich in Germany.
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  He's also a member of the ESMO faculty group for Hematological
• 0:45
  malignancies, the president of the German Lymphoma Alliance,
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  and a member of the Executive Board of EHA.
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  Welcome, Professor Driving, and thank you for being with us
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  today. Thank you.
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  So Professor Drilling is a renowned expert in lymphoma and
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  his work on innovative therapeutic approaches for
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  lymphoma, particularly mantle cell lymphoma.
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  So we are here today to revisit your career and understand how
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  did you get to where you are today.
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  So can you please tell us what is your first memory of
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  hematology? Oh, that's easy.
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  So, so I, I first of all have to give a disclosure, which is, you
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  know, my career went all against the odds.
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  So, so probably I'm I'm not the perfect role model.
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  But anyway, how did it happen? How did I come into hematology?
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  It was rather clear that I did not want to become a
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  hematologist. I wanted to become a
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  cardiologist. And so I was rotating through
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  general internal medicine. During my rotation, I, I got on
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  the oncology ward and at that time I really learned that first
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  of all I got very well connected to our patients and my personal
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  role model was the attending physician who did an excellent
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  medicine. I thought was really taking into
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  consideration also human aspects from patient side, but also very
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  broadly integrating the therapeutic team including the
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  nurse stuff and so on and so forth.
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  And that is essentially where my starting point was, so.
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  You you fell in love with hematology or.
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  In Germany, hematology and oncology is together, which is
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  unusual in the rest of the world.
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  So anyway, at that time for oncology it was rather sobering.
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  You had very few cytoesthetic drugs and there the lymphoma in
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  general were really the inspiring field because there
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  you had some effective treatments, you could cure
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  patients and, and this was a strong motivation.
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  I so I, I really got touched by the field of lymphoma and drawn
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  into this field more and more and that really somewhat brought
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  up my interest in the field. So you enter hematology through
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  lymphoma from the start. Absolutely.
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  And then it was not straightforward because then I
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  went back to the General Hospital, went back to to
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  university. At that University Hospital in
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  Munster, it was 90% acute leukemias.
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  But that was more or less reiterating my focus in that way
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  that I, I was more into the lymphoma and there is some,
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  some, I would say emotional aspect to that.
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  That was really, you know, this subject where I was burning for.
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  So you have worked in different types of lymphoma.
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  Can you tell us what have been your most important findings in
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  different types of lymphoma? If people hear my name, they
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  probably associate me to Monticello lymphoma, but then
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  again this just came by chance in the 90s.
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  I have been in US working on a new tumor suppressor gene P16
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  called at that time nowadays CDK and two.
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  And we just by chance pulled out three cases out of the fridge at
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  University of Chicago and analyzed them.
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  And two of these three cases had P16 deletion.
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  And, and these three cases happened to be Monticello
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  lymphoma. And when I came back to Germany,
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  the head of department at that time said, Martin, you know,
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  would you like to take over on this red lymphoma subtype called
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  Monticello lymphoma? And at that time, you have to
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  understand nothing worked in Monticello lymphoma.
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  So we started with a a phase three trial, a randomized trial
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  and we submitted this proposal to some funding bodies and they
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  said you can't perform phase three studies because you can't
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  define the control arm. There is none, nothing works in
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  Monticello. So that was obviously 30 years
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  ago now luckily the field has changed and there were a couple
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  of revolutions. Probably the first part was
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  integration of the anti CD20 antibody.
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  Lot of today's youngsters take that as you know normal, but it
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  was not at all at that time to establish that.
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  Second thing probably was the establishment of dose
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  intensification and that covers both integration of site
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  Arabine, a drug we know from acute myelod leukemia and also
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  autologous stem cell transplant. It's standard first line study
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  again that happened 10 years ago.
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  And where are we right now? Well, now we cut down
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  chemotherapy. We just go the opposite way.
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  And why is that? Well, the batteries, the enemy
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  are the good one. And now we have better targeted
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  treatment. And so we were successful to
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  establish a new standard of care in younger patients skipping
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  auto stem cell transplant. And I'm privileged to to chair a
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  European network focusing on this kind of disease.
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  And this is what I do believe in teamwork, working together.
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  This have some additional benefits for all of us.
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  You're touching on the fact that you have made a big contribution
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  on molecular targeted approaches with inhibitors like ibrutinib,
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  visceral receptor pathway inhibitors.
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  What can you tell us about ibrutinib and it's use now on
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  mental cell lymphoma? Well, what I can tell you is, is
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  how basic science and clinical care you know gets hand in hand
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  and and that is probably what is still today fascinating for me
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  in hematology. So the first point in Montel
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  cell lymphoma was identifying the cyclin D1 overexpression as
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  a specific marker to recognize these cases.
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  Initially we misdiagnosed 2/3 of the cases.
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  The the majority and this is in effect based on on regulation of
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  cell cycle and in fact the the already named tumor suppressor
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  gene P16. This does also uncoordinate cell
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  cycle regulation well. Meanwhile, we have for example,
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  compounds who inhibit cyclin U1. The first study was had been
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  performed in in Monticello forma by our New York colleagues, but
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  it never took off. The results were good, but then
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  the companies moved on to to breast cancer.
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  Another example is although it's not yet that well established,
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  P16 is one of the strongest prognostic markers in Monticello
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  forma like P53. And now we know that these cases
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  probably specifically benefit of the compounds you mentioned the
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  Brutons kinase inhibitors and ibrutinib is the first
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  generation drug which is registered in Europe for for
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  Monticello lymphoma. And this especially benefits the
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  high risk patients, the patients with for example, P53 rotations.
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  So that tells you a little bit how you know from wet lab to
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  clinical application these developments goes hand in hand
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  and that is what I found very fascinating about these kind of
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  diseases. Are you using other targeted
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  therapies for low grade manter cell lymphoma or?
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  Well, it's funny, as you mentioned it, follicular
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  lymphoma let's say is my origin if you want so, so, so this is
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  where I started off. And this is the kind of lymphoma
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  subtype which is mostly sensitive to old fashioned
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  chemotherapy. And then quite a number of
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  targeted approaches has been explored, all of them also in
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  the easy to treat follicular lymphoma.
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  And surprisingly it came up that follicular lymphoma, well, it's
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  not so sensitive to all of these targeted approaches.
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  And in contrast, Monticello lymphoma, which originally had
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  really the background as an aggressive lymphoma subtype,
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  this was especially sensitive to these targeted approaches.
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  So that that tells me the message that you have to remain
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  humble. You do your experiments, you do
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  your studies, you do your research to find out new things
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  and have you have to be prepared for the unexpected.
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  So you have been lately involved in groundbreaking clinical
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  trials, triangle clinical trial or now multiplied clinical
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  trial. What can you tell us about this?
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  Well, Triangle is, is a huge trial and with almost 900
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  patients, which is extremely challenging in such a rare
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  disease. And why did we come up with this
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  huge numbers? Well, we're talking Europe,
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  Europe is not speaking with one voice but with multiple.
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  So we could not agree on the quote experimental arm.
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  So, So what to test either ibrutinib plus standard of care
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  or even substituting for autological stem cell
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  transplant. And so This is why this huge
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  number of patient has came up and this was only feasible in
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  close collaboration of 14 different national study groups.
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  So this is really all over Europe.
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  And now by these huge patient numbers, we also have reliable
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  data proving the superiority of the ibrutinib containing arms.
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  And these data are so strong that we went back to the company
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  and said we are so convinced, we want to go on to bring that to
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  registration. And exactly this is now going
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  on. And that's for me also the first
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  time ever when we have been so successful that we're moving on
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  from an academic trial to a full registration, establishing a new
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  standard of care. And this is where I'm a little
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  bit proud of. But this is not about me.
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  This is about the teamwork that our consortium, because of this,
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  its size, because of its collaborative nature, we are
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  able to perform these huge studies and our US colleagues
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  looking at the results and, and so I'm very honoured that also
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  at this meeting, don't get that wrong, this is the American
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  Society of Hematology. So this is there if you want
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  some national meeting. Still it's more or less the
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  world meeting. They invite the world to present
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  their data and these results of the Triangle trial you mentioned
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  is now being also integrated into the American guidelines,
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  the NCCN guidelines. So you have mentioned a few
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  times the importance of collaboration.
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  So these trials involved in Europe, 14 countries.
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  So during your whole career, I think collaboration has been
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  really important. You have been a member of many
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  medical societies and one of them EHA.
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  You have been a very active member.
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  How did you get into EHA in the first place?
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  Again, I already told you in Germany haematologies and
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  oncologies together. So previously I have been
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  responsible for haematological guidelines for ESMO because they
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  are mostly oncology. So they have no clue on
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  haematology. And this is where I, I really
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  became enthusiastic about the European Corporation.
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  And then obviously my home institution is ER very clearly
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  been said. And luckily I was invited to, to
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  also being involved in the development of the ER
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  guidelines. And and that's if you want.
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  So my baby at EHA and I'm mean more and more move from basic
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  research to clinical research, I have to admit.
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  And I realised that he has also very strong in the political
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  field. So I become the chair of the
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  initiative against bureaucracy in clinical trials, because
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  performing clinical trials now became so formal and so
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  laboursome. And here I'm talking not about
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  providing safety to our patients.
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  I, I'm talking about pure paperwork that it's hard to
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  perform these huge academic trials anymore in Europe.
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  And that is why I also like E ha.
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  E ha is not only supporting research, not only supporting
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  the setup for the next generation, namely young EHA,
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  but also exploring these political aspects and, and, and
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  strongly lobbying in Brussels. And this, I think is the right
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  way. Again, going hand in hand,
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  science, clinical education, but also these political
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  initiatives. So you mentioned that you are a
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  member of ESMO faculty. So you were a member of ESMO
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  before EHA? Yes, I have been.
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  So how have these two things been hand in hand?
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  Because, as you mentioned, you're now at the initiative of
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  making the guidelines together between ESMO and EHA, what has
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  been your involvement in both societies?
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  That's a good point because I have been the translator to
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  bring these two different worlds together.
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  And in ESMO, I'm the exotic guy because I'm into hematology now
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  in ER, I'm also well, well with Monticello Informa anyway,
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  you're always exotic. So I, I, I live in both worlds.
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  And, and so I was able to bring this initiatives together.
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  I was luckily able to convince ER that it's really important to
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  have guidelines. And I strongly believe in
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  European guidelines. They have different functions.
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  Our national guidelines are very much focused on the different
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  national set up when it comes to registration, health system and
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  so on and so forth. The European guidelines have a
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  totally different function. They also have well, first of
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  all, a broader consensus, but also support different
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  countries, the not so well of European countries.
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  I mean, I'm lucky I'm, I'm, I'm living in, in Germany, which is
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  one of the most wealthiest countries in Europe, to be
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  honest. But we have to be aware in the
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  southeastern part of our continent, they are countries
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  which are much well off. And and for these countries,
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  it's extremely important and helpful to refer to what we
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  assume as really the European standard of care.
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  How do you see the informal research evolving in the next
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  few years? Well, first of all, I think we
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  are rather competitive here. This is one of the few medical
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  fields where the traditional European strength, the
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  establishment of national study groups have really led to some
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  huge effort of research, of improvement of medical care,
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  full stop. How is the field moving on?
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  We are moving away from cytostatic plain cytostatic
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  chemotherapy. Immunotherapy is a huge subject
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  in lymphoma. This is the first broadly
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  introduced gene therapy in medicine with cartesols.
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  So that's really, you know, very innovative.
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  Also we, we take this just for granted.
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  No, it, it hasn't been there a couple of years ago.
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  Secondly, we are moving into the field of of targeted therapy,
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  which is so efficient that it's not only better tolerated, but
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  it's also more effective than plain chemotherapy.
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  And an example is is CLL chronic lymphomatic leukemia, which is
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  also some kind of indolent lymphoma.
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  And there we already said farewell to chemotherapy even in
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  frontline therapy. And this is exactly the
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  direction we I am hoping for also in other kind of lymphomas.
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  So with all these new targeted therapies, immunotherapies, the
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  future of lymphoma is looking better than you could have
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  expected maybe when you started working on this.
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  Absolutely. The field totally changed and we
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  still have to be aware. To be honest, we are all human
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  beings. We have a certain time where we
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  can blossom and push the wagon forward and then other people
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  have to take over the next generation.
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  And this is what I also. Like about ER, ER is a young
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  society. ER is especially focusing also
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  on the next generation and that's really important.
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  And a significant part of our members, around 40% or so are
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  part of this young EHA. So this is what I also really
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  not only like but love about ER, that it looks into the future,
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  not only which direction are we going, but who is going forward.
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  How can we support? And absolutely.
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  And that's also a lot of fun, to be honest.
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  So you have worked as a researcher, you work as a
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  clinician, obviously, and you have been involved in all of
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  these trials and so many initiatives.
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  What do you enjoy the most in your work?
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  This is a difficult question and and as you were saying, I, I was
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  somewhat moving my focus. What I love about my work is
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  really the mixture of it all. So I love also to give students
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  courses. So I'm arranging the study of
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  medicine in our institution. Two people, one surgeon, 11
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  conservative medicine doctor and I'm the the the conservative Dr.
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  And I love to work in a team also on the ward.
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  I love to to stand by our patients, trying to find the
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  best way for them. And sometimes our treatment is
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  only help, but it's just being with your patient.
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  I love to do some research. As I said, I moved from basics
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  research now more and more to clinical research.
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  But clinical research is also translational research.
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  If we're using targeted treatment, then we also have to
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  be much more aware about the genetic alterations.
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  So I think the whole package is a full bunch of flowers.
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  It's so colourful. And we personally, I I'm
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  strongly believing in, in teamwork, but all these
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  different aspects around this is what it makes really great to
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  work in the academic setting. So at the end of the day, what
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  you mean is that really all aspects are important and they
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  all can be enjoyed and they have to come together.
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  So you enjoy the fact that they come together?
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  Well, it doesn't have to come together for everyone, so
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  everyone starts with a focus and and and and and that absolutely
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  fine. It's same for me as well, but
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  but I I love this profession because it's so colorful.
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  Yes. Well, thank you very much for
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  sharing your career story with us and thank you for all the
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  contributions you have made to this field.
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  Thank you also to all of you for listening and stay tuned for our
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  next episodes.