Latest / EHA Unplugged / A Multiple Myeloma and MRD Pioneer: EHA 2025 Lifetime Achievement Award (Prof Jesús San-Miguel)

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A Multiple Myeloma and MRD Pioneer: EHA 2025 Lifetime Achievement Award (Prof Jesús San-Miguel) · EHA Unplugged

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  We did medicine to cure and hematology is probably one of
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  the most fascinating specialities because it combined
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  biology and clinic and most of the developments in oncology can
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  start in hematology. And I would recommend my final
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  message to many of the students of medicine to become
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  hematologist because this is a fascinating speciality and EHA
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  is doing a lot just to make this speciality one of the best
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  opportunities for all of us. So welcome to EHA Unplugged, the
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  official podcast channel of the European Hematology Association,
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  EHA. I am your host, Isabella Livera,
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  and today's guest is Professor Jesus Miguel.
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  Professor Jesus Miguel is a professor of medicine,
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  hematology and currently senior consultant at the Cancer Center
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  of Clinica Universidad de Navarra in Spain.
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  He has devoted his life to improving the diagnosis,
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  treatment and monitoring of multiple myeloma patients.
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  With over 1000 publications, he has shaped modern myeloma
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  research and treatment. He is the recipient at this EHA
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  2025 Congress of the EHA Lifetime Achievement Award.
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  So congratulations, Professor San Miguel.
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  Thank you very much and thanks for the opportunity to be here
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  with you today. Welcome to this podcast.
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  So in this podcast, we're going to be discussing first review
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  your trajectory and see how your key scientific discoveries
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  connect with the advancements of the field.
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  And then we want to have a little look of how the multiple
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  myeloma field is now and what are the treatments available and
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  what are in your opinion, the future directions of the field.
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  So to start on your trajectory, can you tell us about what
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  inspired you to work on multiple myeloma?
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  If you allowed me to to go back in my trajectory, yes, I would
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  say that I was not planning to be a doctor.
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  This has happened many times in my life.
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  Plans have changed. I was planning to be an
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  architect, although I have not a spatial visual, but my father
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  was a vet and he constantly repeated to me medicine is the
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  most beautiful profession. One day, another day.
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  Then I decided OK, let's stop him to talk to me about this, I
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  will do medicine. This was the first.
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  Second is why I became hematologist.
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  OK, then I will come why I became interested in the
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  multiple myeloma. But before why I became
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  hematologist, I was doing my studies at the University of
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  Navarre and I was just waiting for the last exam.
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  The last exam was a general exam on medicine and there was one
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  professor that examed you about this, and this curiously was the
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  professor of hematology, Professor Borrasca.
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  I was waiting in front of his door and a resident that now
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  then become very good friend, a resident of hematology, yes,
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  Cross. And he asked me what are you
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  doing here waiting for the exam with your boss?
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  And he said to me, he's going to ask you about paroxysmal
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  nocturnal hemoglobinuria. What is this?
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  I never heard about that. No, we have seen the first case
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  in all institution and this is hemolytic anemia with the urine
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  is very dark, similar to coke and blah blah.
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  OK, I went into the exam, Professor Borrasca start to ask
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  me about how to treat acute renal failure, diabetes type 1
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  other questions and he said OK, very good, but do you want to
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  get the maximum score in the exam?
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  You need to ask to answer me this question.
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  What do you know about paroxysmal nocturnal
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  hemoglobinuria? The resident told me that the
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  name was PNH. OK, I say please can you repeat,
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  Can you repeat the question? Yes.
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  What do you know about paroxysmal nocturnal
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  hemoglobinuria? So I'm not sure.
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  I think the the name is they also call HPN.
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  No, no PNH. Oh yes, sorry, sorry.
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  PNH. I'm not sure.
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  I think is hemolytic anemia that the urine utriacidosis is very
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  dark in the morning, similar to coke.
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  What are you planning for the future?
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  What do you want to be? I say I was thinking in
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  endocrinology, cardiology. No, you will become
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  hematologist. I say no, no, I'm not planning
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  to do him. No, no, no, there is no
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  discussion. You will become a hematologist
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  and you will move with me next week to Salamanca.
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  I got the, I have just got the chair in Salamanca and you will
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  move with me to build up the hematology department there and
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  you will come now with me to see the first patient we have seen
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  with this disease. Brilliant say I didn't say
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  anything. Then later on I explained to him
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  that was just by chance that I know it, but chances sometime
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  change your life. And in fact this was my case and
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  something similar. Why they become interest in
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  myeloma? I was a resident in Salamanca
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  with him. We were building up the
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  hematology department. Until that time there was not
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  hematology department, there was only biology, not clinic.
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  And I asked him professor, I want to do a PhD thesis.
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  He he was a clutter, OK. He was mainly interested in
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  hemostasia and most of the PhD thesis students there were doing
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  the thesis on hemostasia. And he said I have just read a
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  paper on multiple myeloma and subclasses immunoglobulin.
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  Why you don't do it in this topic, I say, But nobody's doing
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  that here in the department. Someone should start to do it
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  and this was the reason why I start to be engaged with
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  multiple Maloma. As you can see, life drive you
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  to different corridors and the only thing that you need is to
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  follow the right corridor and to be enthusiastic in your work.
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  Once you get into it and you become really good at it, then
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  it becomes really something that you really enjoy doing.
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  For Sartre used to say that life does not consist in doing what
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  you like. I like it what you do.
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  Liking what you. Do exactly and this is
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  definitely. You're a perfect example of
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  that. Can you also take us back of
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  what was the management then of multiple myeloma patients all
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  the time? I can also make another
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  confession. As I mentioned at All
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  department, the most brilliant people were dedicated to
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  hemostasia and thrombosis and also to malignant hematology,
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  but mainly a good leukemia, A lymphoma.
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  Nobody was interested in multiple myeloma and the reason
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  was very simple. Myeloma was an incurable
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  disease. Only one drug melphalam, how we
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  treat the patients with melphalam continues.
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  Melphalam we stop sometime mephalon would reintroduce again
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  mephalon. There was nothing else.
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  Mephalonicorticosteroids. The median survival of myeloma
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  patient was around 2 years. Miserable disease with acute
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  renal failure, with chronic renal failure with bone disease,
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  fractures, devastating disease. And this was in the early 90s.
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  Then the autologous transplant came on and changed quite a bit
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  the outcome of myeloma patients, but it was also based on the
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  same drug, the melphalam. There was no other drugs really
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  efficient for myeloma treatment at that time.
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  So you have been instrumental in the development of five drug
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  combinations for multimodal myeloma.
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  What can you tell us about how this came in in time and how
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  they changed the management of multiple myeloma?
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  OK. I will never forget when we
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  started to work with bortezomid, but just before that thalidomide
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  has emerged in the market as an active drug for myeloma.
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  At that time thalidomide was out of the market.
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  As you know there was responsible for all these
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  childbirth problems and it was only used for leprosery.
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  But due to angiogenesis, it was discovered that the capacity of
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  unkangogenic role of thalidomide and this clearly changed the
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  feel of myeloma. This was the first
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  immunomodulatory drug. Immediately, almost in parallel,
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  a proteasome inhibitor Bortezomib that they started to
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  be called PSC 341 was discovered.
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  And we were very lucky just to participate in the first clinic
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  in the early clinical trials in relapsed patients.
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  But probably one of the most challenging situation when when
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  we decided to combine Bortezomib with melphalan in newly
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  diagnosed patients, non transplant candidates.
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  And for the first time we saw that it this combination was
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  able to induce complete response outside of the transplant.
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  Until that moment, only the transplanted patient were able
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  to eradicate the paraprotein, but with the combination of
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  Bortezomib, the methyl and Prednisone, 30% of the patients
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  achieved complete response. But we paid a tribute for that
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  because peripheral neuropathy was a side effect that was
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  unexpected at the beginning and complicated the life of the
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  patients. But we learn how to handle this
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  moving from twice weekly to only once a week.
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  Bortezomib by reducing also the dose and now the potassium
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  inhibitors is part of the treatment of the skeleton of the
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  treatment of myeloma patient together with immunomodulatory
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  drugs and the corticosteroids. This was for me one of the the
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  the most amazing situation. Then we will be part also of
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  other drugs particularly with pomalidomide to have
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  pomalidomide being a proof in multiple element for for late
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  relapses and then for early relapses.
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  And probably the the most recent one is the CAR T stories using
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  CAR T's, particularly one of the CAR T's cell in late lines of
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  therapy basins that have no other options at that time.
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  After 5-7 lines of therapy, the spected media survival for those
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  patients was 5-8 months survival.
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  And now the report is that five years after initial treatment,
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  1/3 of the patient are progression free.
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  Can you imagine? Yes. 30 percent, 33% of the
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  patients five years progression free in a situation that they
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  have no options. And we have also the conjugated
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  antibodies Antimap, we have the biospecific antibodies several
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  estimable limbo set them up and Ranatama several.
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  And we have the opportunity to target to antigens now.
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  I mean the field is moving, the field is changing.
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  All of these treatments target BCMA.
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  This is funny because one of my first presentation, a task on
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  immunophenotyping was on the expression of CD10IN multiple
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  myeloma and CD19 and CD20. Because until that time, we
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  consider that the plasma cell was antigenically silent, no
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  expression of antigens, but we showed that there was some
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  antigens and this was key for minimal recidal disease studies,
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  OK. And now we know that the plasma
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  cell express several antigens that are really very important
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  for the treatment that you choose.
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  We have the CD 38 antigen, we have the BCMA, we have the GPSA
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  5D, but we have also city 19, we have also FCA H5.
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  We have many antigens and we have drugs that target
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  individually this antigen or can target two or three antigens.
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  Then this is the the the future from my point of view.
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  So you mentioned MRD, So MRD is measurable residual disease.
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  You have also pioneered the use of this tool to better diagnose
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  and treat patients, but can you tell us about how important MRD
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  is and how it's being used? Yesterday a colleague remind me
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  that the first patient I published about the potential
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  use of MRD was in 1994, but the the first real paper was in 2222
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  years ago. And in that paper we analyse, we
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  reported the analysis on patients that were in
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  morphological complete response. They had less than 5% plasma
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  cells in the bone marrow, but we didn't know if this plasma cell
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  were normal or abnormal. And by flow cytometry, we
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  demonstrated that if the cells had antigenically in a normal
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  pattern, these were residual clonal cells and these patients
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  although they were in complete remission had significantly
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  lower survival than the patients that were MRD.
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  We call minimal residual disease negative.
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  Then we move also to a sub PCR molecular technique and we
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  demonstrate the same demonstrate that under the cut off of
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  morphological remission, you have still many residual cells.
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  And if you want to cure a disease, you need to eradicate
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  the cells and you need to use the best tools for to evaluate
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  the residual disease. This is something that is very
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  easy to understand in solid tumors.
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  A surgeon that is dealing with the breast cancer, before he
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  finished the surgery, he asked the pathologist how are the
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  borders, the margin are clean and if they say no, he continue
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  the surgery until he get rid of any tumor cell in the margins in
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  the borders. The same occur in hematology and
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  in multiple myeloma. That is your case, you have
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  residual cells. This mean that this patient is
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  going to relax. Then we need to eradicate all
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  the residual cells and we need to work for that.
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  The good news is that last April we presented in front of the
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  ODAC of FDA the result of a huge study including 12,000 patients
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  coming from randomized trials from a consortium between
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  academic center and the industry.
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  Working together, this analysis was able to show that the
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  patient that achieved MRD negativity in the transplant
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  setting in the non transplant setting and that relapse enjoy
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  significantly longer progression free survival and overall
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  survival. And based on these results, the
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  other the FDA approve minimal residual disease as a new
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  endpoint for trial approval for drug approval.
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  Is this important similarly relevant I always make the same
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  example. We are conducting now
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  participating in a clinical trial in which CAR T newly
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  diagnosed patient is being compared with a tolerance
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  transplant. The readout in terms of
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  progression free survival of this trial will take 10/20/15
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  years. Then we will not know if CAR
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  this should be implemented in first line until 15 years from
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  now. But the readout from numerous
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  cell disease will take only one or two years.
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  And if the FDA considered that this is a valid endpoint, we
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  then will have the opportunity to use the new drugs much early
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  on. And now MRD is being done also
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  on circulating plasma. Cells.
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  Plasma cells. Not in, not necessarily in bone
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  marrow biopsy. So it's becoming easier to
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  follow during time, Yeah. Which is here we try to spur the
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  timing between the bone marrow exams and in the middle we use
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  the circulating tumor cells or the massive spectrometry, both
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  techniques. So all of these developments
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  have been thanks to big collaborations as you've just
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  mentioned. How can you give us an idea of
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  how important it is that people collaborate across the field to
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  bring these results to the patients?
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  Quicker and I think there are two days in life that are
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  critical. One is the the day you are born
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  and the second is the day that you know for what had you been
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  born better? For whom have you been born?
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  And if you are a doctor, you have been born to help the
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  patients. But if you want to help the
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  patients first. You want to help your colleagues
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  because a team is not a group of people that work together, it's
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  a group of people that trust each other and is able to to
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  help the others. For me, this is the most
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  important part of my work philosophy, to try to build up a
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  good team work, making the people happy in the work.
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  And when I say this, I have the fortune to be working with very
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  brilliant people that now they are leaders in the field,
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  extremely well recognized. Some of them are also head of
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  the department, the important departments in Spain.
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  But together with them there has been a lot of anonymous
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  hematologist. They're not in the podium, but
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  they have worked very hard to consolidate the team work and to
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  help the others. And when I see these people that
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  they are proud of the others that are in the podium, I always
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  think the same. Are the people in the podium
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  also proud of these people that is doing general hematology?
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  And I can't tell you. Usually the answer is yes.
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  And for this reason, people can be together and can get the best
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  of each other. What I think is the final, the
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  final goal of the head of the department, just to try the best
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  of each one and to help them to spend 8/10/12 hours in the world
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  being happy and going home happy because it's a disaster if you
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  are not happy in the many hours that you spend in your work.
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  For this reason I think it's it's critical and we need to
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  educate the new leaders not to think that at the end of the
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  career they will be judged for the papers that they have
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  published. This is Robbie's.
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  They will be judged for the people that they have helped to
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  grow and to be happy in the work.
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  And this is what I feel is what I think.
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  I'm not. I'm not sure if I am correct or
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  wrong, but I feel more and more that this should be the
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  commitment of the leaders in hematology.
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  So the new HA guidelines on multiple myeloma are being
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  presented now at this Congress. What is new in these guidelines
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  that you would like to highlight?
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  OK. I think the the always when we
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  create a new guidelines, we think in all the hematologists,
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  sometimes the guidelines can be oriented to the groups that are
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  leader groups in the field that has opportunity to use all the
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  drugs. But in the guidelines, it's also
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  very important to think about those centers that have not
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  access to so many fancy drugs. And this is very important
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  because there are many, many centers, many, many countries,
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  emerging countries with economical constraints and
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  using. You need to demonstrate in the
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  guidelines also that some of the combination, triplet combination
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  are efficient, no, so efficient as the quadruplet and I think is
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  one of the goals of the guidelines.
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  Also in the guidelines we talk, we have not talked about the
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  early disease intervention, early detection because of time
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  constraint. But it's I think also one of the
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  most important fields that we should move on to treat early on
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  myeloma as we do with the solid tumors.
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  So as you look back into your career, what brings you most
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  hope now for the patients and what do you see coming that is
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  really promising? OK.
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  As you probably have seen through this interview a bit
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  sentimental progress in myeloma has been enormous.
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  We expect a progression free survival with a quadruplet
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  transplant of more than 15 years.
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  Outside of the transplant, the progression free survival with
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  the first line is going to be more than 10 years.
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  But still there are patients with very high risk disease that
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  we need to improve. And in any case what the patient
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  need is that the doctors understand what are they their
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  feelings, what are they needs because there are patients that
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  want to fight for any treatment that is able to eradicate the
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  disease. Other patients need just to
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  control the disease and to avoid as much as possible the
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  continuous visit to the hospital.
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  You should sit in the other side of the table frequently to know
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  what the patient desires are, in order just to give him the best
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  possible solution. And I always try to finish my
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  consultation with the patient, saying the same words, probably
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  a bit repetitive. Could I do something else for
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  you? So what do you want to add for
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  the audience that I have not asked you?
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  This is a fascinating speciality and IHA is doing a lot just to
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  make this speciality one of the best opportunities for all of
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  us. Thank you very much for being
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  our guest today. Yeah, it's been a pleasure going
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  through your career with you, Professor San Miguel.
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  Thank you to our audience and please stay tuned.
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  Thank you very much has been my pleasure.