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How Experts Treat Large B-cell Lymphoma (LBCL) · EHA Unplugged

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  We will cover the second line really world change completely
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  with Gardice cells. So Gardice cells now are in
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  second line with laser cell and axis cell and then in the
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  accommodation we propose axis and liser cell in second hand
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  for patients eligible to cartice cells.
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  So cartice cells are for patients in the collapse and
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  refractory patients collapse within the first year and then
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  for the patients that are not eligible for cartice cells
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  Glofigermux or if you are collapsing really late, you may
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  eventually challenge the patients with chemotherapy again
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  and high dose therapy. Please autologous same as home
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  conditions welcome. To EHE Unplugged, the official
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  podcast channel from the European Hematology Association
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  EHE. In this episode we are joined by
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  Professor Maya Jose Kirsten from Amsterdam University Medical
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  Center. I'm by Professor Catherine
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  Teblumun from the Hospitals Only in Paris.
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  Together, they will discuss the recently published EHA guideline
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  for the diagnosis, treatment, and follow up of patients with
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  large B cell lymphoma, LBCL. They're here to give you an
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  overview of the guidelines and help you navigate the panel's
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  recommendations. Welcome and enjoy this episode.
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  Hello, I'm Catherine Tibermo from Paris Sunway Hospital.
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  Hi. I'm Maria J Kirsten.
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  I'm from Amsterdam. We worked together very hard to
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  get this guideline on. We'll discuss all the insurance
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  and outs of the guideline. So this is guidelines about
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  largely selling from us and the first step for the the work up
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  of the patients is about staging the patients.
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  So, so how do we stage the patients for large B cell
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  lymphoma? The first thing is to base the
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  strategies based on the IPI. So we still use this
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  international pomastic index based on the five factors.
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  So the age of the patients which is really important, the
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  interest level, the stage, the number of external sites and the
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  performance status and the performance status is really the
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  key to stratify the patients regarding the choice of the
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  treatment that we will administer to the patients and
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  make a choice. So the three key factors are
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  age, personal status and extensions of the disease with
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  the stage, the external sites and the number of these external
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  sites. Yeah.
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  And if we go a step back, because of course first we need
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  a diagnosis, so we recommend excision of a lymph node.
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  I think we had a lot of discussion about that.
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  What's your opinion? Should we do needle biopsies or
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  should we excise a whole lymph now?
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  So there is a different school, schools for that and the
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  technosis is of course based on this biopsy either which was the
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  surgery or the core needle biopsy.
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  This is a really easy to take the second strategy and to have
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  a coordinated biopsy, really easy to get peripheral biopsy,
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  peripheral leaf node biopsy, profound sites for the biopsy.
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  And this is I think better compared to the surgery.
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  Why? Because the surgery make make
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  will take longer time to get the diagnosis and sometimes we do
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  not have this time when we treat aggressive disease such as large
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  be selling from us. If if possible and not too
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  difficult to reach, I think a whole lymph node is probably
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  better. Gives you more information on
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  the architecture. Yes, yes.
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  So, yeah. And particularly the micro
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  environment, we know that with the new drugs now we need to
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  have informations regarding the micro environments.
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  It's always better to have this surgery biopsy, but if it's not
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  possible, of course coordinated biopsy is really important and
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  important step. And what do you think are the
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  minimal methods that need to be used to get to a diagnosis at
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  this point? Which methods, immunochemistry
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  or molecular methods are really necessary?
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  Yes, of course we need to have between high grade B cell
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  lymphoma transform from indolent lymphoma as follicular
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  meshalzone lymphoma as primary B cell lymphoma that are really
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  particular lymphoma. So we need to have
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  immunochemistry. We need to have also FISH
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  diagnosis regarding genes such as Mick B cell 2B cell 6 and to
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  have eventually the subtypes regarding ABC or GCB which is
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  not now considered as nobligratory marker because we
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  know that there is no difference in term of therapy strategies
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  between AB, CS and GCBS largely selling from.
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  What do you think of NGS to look at mutational landscape in the
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  tumor cells? Yes, it's really important and
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  interesting to have these markers, but right now we have
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  no difference in term of therapy strategies based on NGS.
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  I think that we will see more evidence of targeted agents
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  being more more active for example in the MCD type is, but
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  this is at the moment not we didn't make it part of of the
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  guideline because it's not black and white.
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  So we, yeah, we cannot do this in an evidence base then?
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  Exactly. Maybe in the next round of the
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  the guidelines, maybe in the future, in the near future.
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  I'm sure not right now. Yeah.
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  And what do you think is the strategy in terms of imaging
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  diagnosis and for AS into a more end of treatment evaluation?
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  Yes. So as we said at the baseline,
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  it's really important to have a good aspect on the extension of
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  the disease and even the master bulky and to measure the bulky
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  more than based on the CT scan. But also the PET scan may afford
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  to have a better evaluation of this bulky mass PET scan at the
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  baseline. And then the PET scan may also
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  be repeated with interim analysis after 2 cycles, 4
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  cycles, and even at the end of the treatment.
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  So if you are doing interim analysis, you may eventually
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  skip at the end of the treatment with PET scan and only do ACT
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  scan. But it's really important to
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  have a sense of the metabolic response assessment, which is
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  really important to know if we have complete response.
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  Do you think that there is several aspect to assess this
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  metabolic response in term of the?
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  Yeah. So at the moment I think
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  standard is that we use the Oval scores or the semi sort of semi
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  quantitative assessment of the yeah, several shades of Gray.
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  So and I think that for the moment is satisfactory.
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  But I think for interim pets we might also start implementing
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  the delta SUV because it has been shown that if at interim
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  pets there is more than 70% decrease in the standardized
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  uptake value, those patients have an especially good
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  prognosis. I don't think that's implemented
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  at the moment at most of the hospitals, but I definitely
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  think Delta SUV and at diagnosis the metabolic tumor volume will
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  gain the momentum in the coming years.
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  This effectively is the strategy to evaluate better the patients
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  during the first line. And so in your opinion what is
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  the first line treatment for the patients with large B cell in
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  from us? So the common patients, what is
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  the best treatment for large B cell?
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  Yeah. So depends of course on stage.
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  So for the limited stage patients and low risk factors, I
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  think abbreviated immunochemotherapy is the
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  standard. So mostly 4 cycles of Archo.
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  Maybe we can even go lower with the negative interim path.
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  But for the stage 2 with Milky disease or stage 3, four, we, I,
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  I remember we had some discussion about what was the
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  best first line. And of course again depends on
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  age, performance status, but also on comorbidities, for
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  example, the cardio cardiacomorbidities, which would
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  make treatment with antracyclins more difficult.
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  But for the standard patients with a low IPI zero to 1, I
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  think Archop 6 cycles is still the standard of care for, I
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  don't know now 25 years or more. So we know perfectly effectively
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  this surface line and based on Archop, what about the high
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  grade piece of lymphoma because we know that Archop is maybe not
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  so satisfactory for these patients?
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  Yeah. So I create lymphomas especially
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  if they are double hit. And as you know now in the new
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  DHL classification, this pertains to patients who have a
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  mid translocation and BCL 2 and it's no longer the MIC and BCL 6
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  or the triple hits. I think they're with regular
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  Archop we don't see a good enough outcomes and also the
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  Polar R chip doesn't seem to be better than our shop in that
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  particular population. So there we would go in a fit
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  patient for those just epoch R or another intensified regimen
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  and also strongly consider CNS prophylaxis.
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  What about what is your opinion regarding this treatment and to
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  whom? I would like to administer this
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  treatment. So in the study, the patients
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  with an IPI of two to five were eligible for for this study.
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  So it's a higher risk population and there was a difference in
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  progression free survive also 6% absolute difference, but no
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  difference in overall survival, probably because we have good
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  selfish salvage options with stem cell transplant or Carty in
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  a second line. So yeah, it's implemented
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  differently in different countries.
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  For example in the Netherlands, but I think also in France,
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  EFOLA is not reimbursed. So we still give our job.
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  And the last question regarding the first line, but we could
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  have a lot of more questions. What about this external
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  disease? Sometimes we have patients with
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  no involvement or few another involvement but external with
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  testes for example. And we discussed the past few
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  years about CNS prophylaxis. So how could we deal with this
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  prophylaxis and external disease?
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  I think that's a whole topic on itself.
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  So much discussion about the use of CNS prophylaxis.
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  I think most centers have abandoned intrathecal
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  prophylaxis. So if you think there's an
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  indication for CNS prophylaxis, I would go for high dose
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  methotrexate. So at least three grams per
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  meter square and two cycles and mostly do it at the end of
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  therapy if there's no CNS involvement.
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  And of course, it needs patient to do a baseline CSF assessment.
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  And yeah, so if you look at the extranodal lymphomas, I think
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  it's best demonstrated for primary testicular lymphoma
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  because they have a very high rate of secondary CNS
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  involvement. So we would definitely do it in
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  those patients. I think the indication for CNS
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  prophylaxis has shrinked over the years.
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  And finally, the last one, because I think it's really
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  important. The strategy is really different
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  from the other large B cell. Lymphoma is the primary media
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  cell lymphoma. What is your strategy for this
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  PMBA? Yeah.
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  Yeah. So these are mostly young female
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  patients who present with a bulky mediastinal mass.
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  And of course also here direct direct comparison in clinical
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  trials is lacking mostly. But if you look at the results
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  of ARCHOP versus intensified ARCHOP like ARCHOP 14 or those
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  adjusted EPOCH R or other intensified regimens, there's a
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  clear difference in the progression free survival in
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  those patients and also very importantly, the rate of
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  complete metabolic remission at the end of the induction.
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  And that's really important because in those patients who
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  still have active disease, you might consider the radiation
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  therapy, but these are young female patients and giving them
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  radiation therapy to the chest might also mean an increased
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  risk for breast cancers. I think achieving the CMR is
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  really important. I think the i.e.
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  LSG did a great job in their study demonstrating that in
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  patients with CMR you don't need radiation therapy and that this
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  is achieved much more often with intensified recommends.
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  That was interesting to see that actually our Job 14 performed
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  more or less the same as even more intensive regimen.
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  So we have started to we did those just at ebook R, but are
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  drifting back to our job 14. How about your SO?
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  This is exactly the same strategy.
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  We know you, we are using our job 14.
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  It's really easy and in this population of patients who are
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  younger after 14 is really and there is no sort of effect,
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  major sort of effect. So yes, we are.
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  We switch the two after 14. Yeah, in the primary B cell in
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  format. Yeah.
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  And then what do you do in the patients who still have no CMR,
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  so either the score four or five?
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  So we can create as you said delta SUV here to be sure that
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  we are really in not a good response and then we biopsy, we
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  try to biopsy the patients and we go to second line if we are
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  not in. Complete response.
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  Yeah. So you wouldn't go for radiation
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  in those patients? We prefer depending on how is
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  the hazardous disease if you have minimal hazardous disease
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  with many I mean a small sites still involved and if
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  hyperfixation we may eventually propose a radiation therapy, but
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  if we have no chemo sensitivity, we will move to.
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  Yeah, I agree. And I think in this in this
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  study that I'll study, they also showed that if you irradiate
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  this DOFIO score 4 cases and there's also a very good
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  response. But another strategy is just to
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  wait and repeat the PET scan. Exactly this, yeah.
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  Yeah, I think we've covered the first line.
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  And then we will shortly cover the second line that we had
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  really world that change completely with the gardice
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  cells. So Gardice cells now are in
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  second line with laser cell and axis cell.
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  And then in the accommodation we propose axis cell, laser cell in
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  second line for patients eligible to CARTES cells and
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  then for the patient that are not eligible for Cartes cells
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  and collapsing. So Cartes cells are for patients
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  in the collapse and refractory patients collapse within the
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  first year and then for the patients that are not eligible
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  to for cartesis glaufygmarks or if you're collapsing really
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  late, you may eventually challenge the patients with
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  chemotherapy again and high dose therapy plus orthologous
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  symptoms transportations. So the choice for this online is
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  really depending on the time of collapse and the sense of how
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  refractory the disease is regarding chemotherapy.
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  Yeah. So in the in different countries
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  this is weighed a little bit differently by also by the HCA
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  bodies. And for example in the
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  Netherlands, the patients in the second line who are refractory
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  or who have early relapse should be transplants eligible to
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  receive CAR T, which I think is a little strange because they're
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  not getting high dose chemotherapy.
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  So they should be eligible for car DI think and not for stem
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  cell transplant. But yeah, hopefully there will
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  be the results of the daily two study and we can re discuss this
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  also with with our healthcare institute in France.
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  It's not a problem. You can.
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  Yes, we can effectively use this strategy for how the patients in
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  early relapse. And then the Sol line that is
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  really improving with the bispecific antibodies, anti
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  CD20, anti CD3 with two antibodies available in Europe
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  and almost all over the world with glofetamab and apreitamabs
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  of both drugs that are changing. Also the result in third line
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  for patients with refractory disease after two prior lines.
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  Yeah. I think in this context, it's
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  interesting the effort which was done by Florence Prusa together
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  with the guidelines. We also actually published their
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  perspective paper in Hemisphere, which was led by Florence.
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  Actually looking at the availability of all those new
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  drugs in Europe. She has shown some, I think more
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  shocking results about clinical trial availability, which is all
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  very different between a different European country, but
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  also to access in terms of reimbursement to these new drugs
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  because there are many countries including ours where for
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  example, by specifics are not yet reimbursed.
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  So we're seeing a completely different picture.
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  Yeah, across, even across Europe, yeah.
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  Thank you very much and thank you to everybody here to have
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  listened to us about these guidelines of large be selling
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  format guided by EHH. Thank you very much.
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  And thank you to the audience for listening.
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  And if you enjoyed this episode, please like it and subscribe to
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  our channel. Stay tuned for more episodes of
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  EH. Unplugged.