Latest / EHA Unplugged / How Experts Treat Peripheral T- and NK-cell Lymphomas

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How Experts Treat Peripheral T- and NK-cell Lymphomas · EHA Unplugged

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  These guidelines today have much more clinical trial based
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  evidence than guidelines from 10 years ago, even if it is a rare
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  disease. And we have introduced in the
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  first line a more refined application of standard tools
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  that existed so far. Welcome to EHA Unplugged, the
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  official podcast channel from the European Hematology
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  Association EHA. I'm your host, Isabella Olivera.
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  Today we're talking about the recent ESMO EHA guidelines for
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  peripheral T and natural killer cell lymphomas.
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  This is a collaboration between ESMO and EHA.
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  To walk us through these wide lines, we have today 2
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  professors, Francesco Lamore from ESMO and Massimo Federico
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  from EHA. Professor Damore is a clinical
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  professor and chair of the Department of Hematology at Arus
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  University in Denmark. And Professor Massimo Federico
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  is a senior professor of medical oncology at the University of
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  Modena and Radio Media in Italy. They were both deeply involved
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  in shaping these guidelines, and they're here to help us
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  understand what's new in these guidelines, why these changes
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  matter, and how they can make a difference for patients.
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  Thank you for being with us today.
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  Thank you for your invitation. Thank you for invitation.
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  We're going to start by clarifying which informants are
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  in this guideline that uses the term PTCL to cover malignancies
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  that are derived from either T or NK cells.
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  There are many two types what is covered in this guideline.
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  These guidelines cover the different peripheral T cell
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  lymphomas that are classified as a nodal, extra nodal, and
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  leukemic disseminated. We did not cover the topics of
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  cutaneous peripheral T cell lymphoma.
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  We did not cover the pretymic either, that is the T cell
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  derived acute lymphoblastic leukemias and lymphoblastic
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  lymphomas. So it is the mature entities,
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  postymic with the exclusion, as Professor Federico just said, of
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  the cutaneous one among the mature entities.
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  And why was there a need for this new guidelines?
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  The last guidelines were that the community received in this
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  context were produced in 2015. A decade ago landscape of
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  peripheral T cell lymphomas, T&K cell lymphomas was significantly
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  more simple. But there has been an increase,
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  a dramatic increase in complexity due to steep growth
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  of knowledge in the in these entities, knowledge about their
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  biology, which also has led to the definition of new entities.
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  As we take for example, the breast implant associated
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  anaplastic glass cell informer was something absolutely absent
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  in the latest guidelines. In the latest guidelines we were
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  talking about intestinal T cell informers that were enteropathy
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  associated type 2 which we called it enteropathy associated
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  but there was no enteropathy around.
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  Today this has changed the name and has also completely
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  different biology and background from the well known and celiac
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  disease associated T cell informers.
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  These are two examples of brand new things, and there are many
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  more to to mention that make the complexity level of these
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  guidelines much more difficult to see and to understand if you
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  if you don't have specific guidelines looking at all the
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  entities. In addition to the clarification
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  of Professor Damore, I would like to also underline that we
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  did our best to offer practical deadlines for more than a dozen
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  of different subtypes just to help physicians to find
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  correctly the deadlines for the specific, for the single
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  patients. So it was really a huge effort
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  to not to offer detailed information on how to treat
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  nodal, different types of nodal extranodal, different types of
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  extranodal and so on. And this was one of the most
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  relevant reasons for the need of an update.
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  The first program I imagine is to diagnose this lymphomas
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  because there are so many subtypes and they are rare.
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  How to diagnose today? What are the recommendations in
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  this guideline? To begin with, as the answer of
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  this question to this question, we have one of the most
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  recognized T cell lymphoma pathologist as a member of our
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  author group, Professor de la Belle that has produced quite
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  detailed overviews and algorithms for the diagnosis
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  which is based on a three level tire diagnostic approach.
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  The first level is the morphology, the second level is
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  the immunohistochemistry as we are used.
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  But then there is 1/3 tire which is the molecular profiling at
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  genomic level which today has entered the diagnostic area no
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  longer as a research topic but more and more interacting with
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  the daily diagnostic decisions. So the genomic profile for
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  example in TFH particular helper T cell derived lymphomas will
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  allow you to make decisions in the in the first line and
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  relapse, relapse setting for example, for the use of hyper
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  methylating agents that are no no longer only for research, but
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  also introduced in the daily practice today.
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  So these are new things that they got the guidelines from
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  2015 did not have at all. And so I would also add that we
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  did our best that we tried also to clarify the complexity,
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  complexity of the initial diagnosis for the needs for
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  confirmation by an expert pathologist and also the need to
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  have a multidisciplinary approach in planning right to
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  treatment according to the subtypes and the extension of
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  the disease. But also we would like to help
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  physicians to treat their patients in the area of
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  residency of the patients. So it's a rare disease.
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  Now it is impossible to imagine that we can cover with the
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  referral center everywhere. So we we have to also to try to
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  combine the the needs for a correct diagnosis and the needs
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  for the treatment not so far from the area of residency of
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  the patients. And this is an effort of of the
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  group to clarify what is essential.
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  First level, second level, third level, the need for discussing
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  the diagnosis, the suspected diagnosis at the referral level
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  and then offered the opportunity to treat the patients as close
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  as possible to their residency. So it is not so easy, but so
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  we're trying to do this. But it's not something that the
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  guidelines can go and, and organize in the, in the text
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  because there is such a heterogeneity of realities out
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  there. And these are guidelines that
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  are, that are read across the world of global guidelines.
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  Although they're European in origin, they will be, they will
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  be read in the, in the Americas, in Asia, in global fashion.
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  So it's difficult to come and organize things that are
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  extremely heterogeneous. It is a rare disease, it is a
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  difficult disease even for experts.
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  And if you have to be treated firstly, diagnosed correctly and
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  then treated, it is important that, as the professor said,
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  Federico said, it is important that a person with experience is
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  looking at these things and a group, A-Team, a
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  multidisciplinary team, where it is possible to have it, is there
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  because that offers the patient the possibility of survival,
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  which is significantly higher than if you're treated standard
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  of care in some kind of discipline, viable environment.
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  So with respect, with the difference, huge difference that
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  there is not only in countries, but areas of the world, this
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  must be said about these diseases because they, they are,
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  they are very difficult. We we had recently a meeting in
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  Asia. In different countries it's
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  extremely different how diagnostic and interpretation is
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  depending on the region you're taught talking about.
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  So the first the big challenge is diagnosis, but then can you
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  summarize how these guidelines approach the treatment in first
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  line? Which are the main points you
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  want to highlight? Yes, the, the, the first line is
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  of course something that needs as much evidence as possible.
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  We are, we work in these guidelines with levels of
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  evidence and in, in the, in the recognized international
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  terminology. And as you can imagine in
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  diseases that are rare, there will never be the big trials
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  with hundreds or thousands of patients like you have in some
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  other some other sections of oncology like breast cancer,
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  colon cancer. This is a rare disease.
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  So there will be small trials. The evidence will be relatively
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  weak and we have to work with that.
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  But these guidelines today have much more clinical trial based
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  evidence than guidelines from 10 years ago, even if it is a rare
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  disease. And we have introduced in the
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  first line a more refined application of standard tools
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  that existed so far. The use, for example, of a
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  chopped backbone CHOP is an abbreviation for
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  cyclophosphamide, hydroxydonor, rubicine, vincristine and
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  Prednisolone, with or without the addition of a topocyte, with
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  or without the use of a stem cell cell transplant of some
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  kind, autologous or allogeneic. But these things were also
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  mentioned in decade ago. What is different is that it is
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  a refined mentioning based on recent clinical trials, based
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  also on world evidence from registries, population base and
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  also from experience with long term follow up.
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  So this refinement is something that we didn't have in the past.
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  We have looked at for example a toposite has been a long
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  discussion in the community. But the, the guidelines now say,
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  we know that a toposite has time after time shown an effect in
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  elk positive ALCL. It it has been shown in
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  prospective trials and it has been shown in several
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  retrospective analysis. So you can, you can say that the
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  use of a topazide in elk positive ALCL is not just at the
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  same level as the other entities.
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  Elk positive ALCL seem to have a predilection, seems to have a
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  specifically good response compared to the other entities.
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  So this is what I mean by refinement of what we told
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  people 10 years ago. In first line therapy, what we
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  clearly tried to do is to offer the opportunity to select the
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  right management, the right approach according to stage of
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  the disease and histologic subtype.
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  And when is better to use CHOP, CHOP, eat a chopper plus a
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  topocide. When adding novel agents like
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  brintuximabedotin in anaplastic large cell lymphoma setting.
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  And also the the more appropriate approach for
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  offering a stem cell transplant at the end of induction therapy
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  in those entities where it is clear that this could be of
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  benefit. Although we are still lacking
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  prospective randomized at the clinical trial.
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  So just for summarizing this aspect of first line therapy,
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  first the panel suggests to consider patients for enrollment
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  in clinical trial. Second, in terms of standard
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  care, those people that like to check for our deadlines have
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  three figures to summarizing the flow chart for patients with
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  nodal extranodal and low clinic disease.
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  So we hope for a lot of opportunities to try to find the
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  right place for selecting treatment for the patient.
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  So just to just to, just to mention on the on the transplant
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  have we have the trials that have been published one year ago
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  2024 showing for example the randomized trial run in France
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  and Germany, the AATT trial published in 2021 in blood and
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  then again now in 2024 with a long term follow up.
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  This information with a with a comparison between autologous
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  and allogeneic transplant in the front line setting was an
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  important information for the community because you you could
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  see and confirmed in both the final analysis of 21 and the
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  long term follow up of 24 that what you gain in terms of better
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  duration of response with a Nello transplant in.
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  In other words, less relapses, lymphoma related relapses you
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  lose on in term of transplant related mortality.
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  So there is a toxicity from the modality which has less relapses
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  at at the end of the day, they balance each other completely.
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  So there is no difference. So this information is important
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  for the community. And this is another example of
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  applying things at at the right time, the right thing at the
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  right time. The guideline ends up if you, if
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  you have a transplant eligible patient saying, well transplant
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  should be autologous in the upfront setting where you don't
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  where you still have the LO option in the relapse setting to
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  salvage your patient if the patient relapses.
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  So this isn't quite important message from from the guideline,
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  which is sustained not just by a gut feeling, but by a randomized
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  trial that has been published in the Journal of Clinical Oncology
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  just 12 months ago. Is there anything you would like
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  to highlight about the second line so the relapse?
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  Setting. Yes.
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  So we started the from the the knowledge that so far the
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  outcome of patients with refractory or relapsed
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  peripheral tisel lymphoma is usually dismal.
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  So there is a need for improvement and the deadlines
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  also offer the best evidence on the new agents that have to be
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  considered for patients with relapsed or refractory disease
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  together with the best use of Autolu stem cell transplant and
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  also other innovative approach. But probably professor for the
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  more already can just underline some specific benefit of new
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  agency in specific subtypes of relapse of the T cell lymphoma.
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  I want to just wrap up on around the approach of the stem cell
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  transplant that in the guidelines you will see
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  autologous transplant applied to frontline approach with some
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  notable exception exceptions For example, the hepatosplenic T
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  cell Informa and the monomorphic epitheliotropic intestinal T
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  cell Informa. The Michael, those two we
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  recommend allogeneic upfront otherwise most of the others
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  nodal and externodal will be would be the recommendation of
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  photologists. Whereas in the relapse setting
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  all chemosensitive patients that are transplant eligible are
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  recommended treated by allogeneic transplant.
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  This is a major pattern and for the leukemic entities that we
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  have in these guidelines, we didn't have them ten years ago.
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  If they are chemosensitive in the three aggressive entities,
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  then we recommend to treat them or consolidate them with
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  allogeneic transplant in the relapse setting.
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  One comment is also a new trend surging significantly in the
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  field of T cell informers of the importance of minimal residual
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  disease. We know minimal residual disease
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  from leukemia, we know it from mental cell Informa, We know it
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  even for a diffuse large B cell Informa.
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  It is a topic that is more and more usual in these discussions.
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  But for T cell entities, it has been a challenge also in this
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  field because the T cell receptor rearrangement clone
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  clonality has not been easy to demonstrate.
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  But today the tool of circulating T circulating tumor
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  DNA, CT DNA really taking speed and, and and and increasing in
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  publications. I just came home from from a
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  meeting a few days ago. There was a huge publication
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  that shows patients we call incomplete remission with
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  standard of care tools today, which is the PET CT scanning
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  metabolic complete remission. Almost half of them that are
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  called CRS by PET CT, they still have minimal as usual disease if
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  you if you look at it with MRD. So actually in shop only treated
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  PTCL in that publication at the end of the day, 29% of the
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  patients treated had MRD negative status at the end of
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  the treatment. So what I'm saying is we will
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  learn in time already, not in time, but it's already there.
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  It's already now we will learn that MRD will give us new way of
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  approaching the disease because what we have been calling CR
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  until now is maybe not CR. Is this already in the
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  guideline? The MRDN.
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  We just mentioned it, but CT DNA will be one of the two topics in
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  my opinion, that will dominate the update of the next
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  guideline. If you, if you ask me what,
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  what, what will happen for in the next guideline?
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  What do you expect to be the new hot topics in the next
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  guidelines? And of course, in guidelines,
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  you cannot have publications that are so recent that you
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  need, you need more confirmation, you need third
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  publication that shows the same. So it takes a little bit of
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  time. Guidelines will always be a
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  little bit the breaking news of of of the field, but I think the
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  next guideline will contain it so.
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  There's this concept of living guideline.
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  Yes, yeah, it is. It is necessary.
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  Otherwise, you know, they become like dinosaurs, they become like
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  some some stone in past, which is very interesting to see from
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  an archaeological point of view. But if you if you have to work
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  with that every day in your clinic, then you would like to
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  have something more living. And the NCCN has done that.
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  We try to do the same. Exactly 1 of the aims of this
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  group of people supported by ESMA is to update guidelines as
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  timely as possible. I don't know if we will be able
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  to do twice the year or three times per year or once in two
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  years. However, once we will have
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  relevant information coming from research being the clinical
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  trials or other biological news. Of course, Francesco and all the
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  group is in agreement with the discuss the opportunity to
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  create an update or to inform the community that there are
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  news compared to the already released deadlines.
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  This is very important it. Must be also easier by the
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  collaboration between ESMO and EHA to keep updating this
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  guidance to join the airports. It's good that societies,
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  European societies show they can work together and we, I mean, it
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  is the first time in T cell informers.
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  But if you look at myeloma, they're just being published the
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  ESMO AI myeloma guideline, common guideline.
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  So there are good examples and other that are continuously
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  produced. Get back to your question about
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  about refractory, relapsed refractory disease.
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  The guidelines also have caught some of the very, very new
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  publications about novel drugs that have been clinical trial
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  based. And just to anecdotally for this
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  podcast, I can tell you we got the results of the clinical
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  trial, the SPIRIT trials by the professor of Chai that published
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  that in Lensity Hematology in the summer of 2000 and it
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  appeared in Density Hematology. Actually I think it was one week
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  or two weeks before we had to send the manuscript out in
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  external review and and we sat in the group.
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  Well, we would like to have this publication mentioned.
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  So it was very last second. We caught that bus and put and
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  put that publication in our references.
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  And it is a treatment of external NKT lymphoma that is a
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  typical nasal type lymphoma present in Europe but more
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  frequent in Asia where the use of checkpoint inhibitor, which
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  is a novel drug in the context of NKT lymphoma.
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  But it has unique favorable effect combined with the usual
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  Aspergenase containing regiments.
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  So if you add upfront, actually this trial was upfront first
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  line, it came on top of results that we already had in small
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  phase two trials in the relapse setting.
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  But this upfront trial with overall response rate of almost
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  80% that that has been completely new in the field.
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  So I'm very happy and a little bit proud that we had this
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  publication included at the last minute in the in these in these
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  guidelines. So Professor Federico, what
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  would be your take away message for the audience?
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  The the most important recommendation in my view is one
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  of you suspect to have a patients with peripheral test
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  cell lymphoma. Please check for a correct
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  diagnosis. This is first, if you are not
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  all the facilities in your area, please connect with the centers
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  that can help you in confirming or not confirming the diagnosis.
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  This is the first step. Now correct diagnosis will
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  translate in the best opportunity to offer the right
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  treatment and the best options for cure.
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  So the second is if you have a patients with a confirmed
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  diagnosis of peripheral lymphoma, consider the
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  opportunity to enroll the patients in a clinical trial.
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  Third, if you have to offer just a standard care, please follow
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  the deadlines. We have recently released that,
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  in my opinion, they have one of the most relevant efforts to
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  help physicians to make the right decision for the patients.
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  And I asked the same question to you, Professor Amore, what would
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  be for you the take away message for everybody to go and read
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  this guideline? Because it's a very complex
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  subject, we cannot cover the whole thing in.
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  I would say to the to the reader of the guideline, the
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  recommendation how to read the guideline is Please.
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  If you mean it seriously, then read the guideline in its
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  entirety. Read the main manuscript, but
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  read also the supplementary of the guideline.
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  The supplementary is only supplementary because there is a
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  limit of words from the journals.
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  The things in the supplementary are important things,
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  particularly in T cell lymphomas where we have so many entities
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  and particularly the very rare entities that many physicians
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  feel a little bit shaky about because they maybe have not seen
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  such a patient ever. So my recommendation is please
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  read the entire guideline. In my opinion, you have not read
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  the guideline if you don't read both the main manuscript and the
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  supplementary as a recommendation for what to do to
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  your pace to your patient with preferred T cell informers.
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  As as it was said by Massimo, by Professor Federico, the the
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  importance of trying to put patient in a clinical trial is
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  just because what happens in a clinical trial is that you have
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  more precision about what's going on.
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  You gather information, you have a monitoring of your patients
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  and those that have looked at it.
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  There are some interesting, interesting studies done on plus
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  minus clinical trial within a certain disease.
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  And there is a difference in in survival, not because the
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  clinical trial was the best clinical trial in the world, but
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  the fact that the patient is monitored and is carefully
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  followed that makes it less likely to have complications
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  that come maybe suddenly without anybody expecting it and also a
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  better care of the patient. So there is an there is an
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  advantage to have a patient in a clinical trial.
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  But the problem is and any reader of the guidelines will of
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  course agree that if there is no clinical trial, which is the
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  most frequent situation you are in, then the recommendation to
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  to bring your patient in the clinical trial is not so easy.
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  And sometimes you can get a clinical trial, you have to send
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  your patient out of the country and that is also a little bit
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  heavy for the patient and the family.
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  But but that, that would be best.
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  And we have highlighted that in the guidelines and importantly
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  that disciplines talk together. So it is important to have a
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  tertiary center. I know there will be different
• 27:12
  realities around the world, but this multidisciplinary approach
• 27:16
  from pathology in one end to clinical, clinical intervention
• 27:21
  in the other end, our treatment will never be better than the
• 27:25
  diagnosis we are offered from the from the diagnostic side.
• 27:30
  If the diagnosis is wrong, our treatment will be wrong or not
• 27:34
  appropriate. So, and I have the impression in
• 27:38
  this particular guideline, the first key aspect is really a
• 27:42
  correct diagnosis because there are so many entities.
• 27:46
  And from what I could see in the guideline also each entity is
• 27:50
  treated in a different way, in a slightly different way in any
• 27:53
  case. So it's key to go and look at
• 27:56
  all the details and be precise. So you know you have a
• 28:00
  heterogeneity here which is practically unseen.
• 28:04
  I know there are variants in mental cell lymphoma, there are
• 28:07
  variants in diffuse large B cell lymphomas, but but these are
• 28:11
  biologically completely different diseases.
• 28:15
  If you think about the lymphoma arising from a breast implant
• 28:19
  and the lymphoma arising from a patient with celiac disease in
• 28:23
  the in the small bowel, these two diseases are so far from
• 28:28
  each other. OK, they derive from T cell from
• 28:31
  T cells, but they are two complete different planets.
• 28:35
  So is there anything else you would like to add for the
• 28:38
  audience? My wish is to ask the audience
• 28:42
  to use the deadlines and in case they need some more explanation,
• 28:47
  contact us and we will do our best also to clarify.
• 28:53
  And I would say to the audience, stay tuned for CTDNA and
• 28:57
  combination of new drugs and combination of new drugs, HTAC
• 29:01
  inhibitors and easy H2 inhibitors, both oral.
• 29:05
  So that is just some teasers for the next guidelines.
• 29:09
  OK, so there. Thanks a lot.
• 29:11
  Thank you to the audience for listening and if you enjoyed
• 29:14
  this episode, please like it and subscribe to our channel.
• 29:18
  Stay tuned for more episodes of EHA Unplugged.