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How Experts Treat Mantle Cell Lymphoma (with Prof Mats Jerkeman) · EHA Unplugged

• 0:00
  Why was there a need for new guidelines?
• 0:02
  So we had the European guidelines written in in 2017,
• 0:06
  but a lot has happened since then.
• 0:10
  We have now number of novel agents that have become
• 0:15
  available both initially at relapse.
• 0:17
  I'm talking about BTK inhibitors that are now also entering first
• 0:22
  line treatment and we also have a number of agents available at
• 0:25
  Relapse, for instance, CAR T cell therapy, important BCL 2
• 0:31
  inhibitors and also novel BTK inhibitors.
• 0:35
  So there was definitely a need for for an update.
• 0:41
  Welcome to EHA Unplugged, the official podcast channel from
• 0:45
  the European Hematology Association.
• 0:47
  EHAI am your host Isabel Olivera.
• 0:50
  Today we're joined by Professor Matz Jerkeman, who is a
• 0:53
  professor of oncology at London University in Sweden.
• 0:56
  Professor Jerkeman has been instrumental on shaping the
• 1:00
  recent EHA clinical guidelines on Mantel cell lymphoma MCL.
• 1:04
  So we are delighted to have you with us today to discuss these
• 1:08
  guidelines and what they mean for clinicians and MCL patients
• 1:12
  across Europe and beyond. So thank you very much for being
• 1:15
  with us today. Thank you for hosting me SO.
• 1:18
  To start off, could you explain what are the main clinical
• 1:21
  features of MCL? Yes, Mantel cell lymphoma is
• 1:26
  something in between the and aggressive lymphomas.
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  It's a it's AB cell malignancy and it can sometimes be very
• 1:34
  indolent and be managed by watch and wait approach actually like
• 1:39
  other indolent lymphomas, perhaps around 20% or so or can
• 1:44
  be managed like that. But it can also be a very
• 1:46
  aggressive disease and that require very intensive therapy
• 1:51
  and especially at at relapse it can be very aggressive and it
• 1:56
  presents usually as lymphadenopathy but often also
• 2:00
  with lymphocytosis and bone marrow involvement is almost
• 2:05
  mandatory, occurs in about 90% of patients.
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  Also, gastrointestinal involvement is characteristic
• 2:14
  for mantle cell lymphoma. How are patients stratified?
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  You were saying that you can have from indolent lymphoma to a
• 2:20
  very aggressive form. So what are the main challenges
• 2:23
  when you have a newly diagnosed MCL?
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  How do you? What are the risk factors to
• 2:29
  take into account? Yes, additionally we have the
• 2:32
  main looked at age because the the the previous standard
• 2:39
  treatment for younger patients at least up to 65 years it's
• 2:44
  been treatment involving high dose cyterabin as induction and
• 2:48
  also consolidation with high dose chemotherapy and autologous
• 2:52
  stem cell support treatment has been divided according to
• 2:55
  tolerability for for autologous stem cell transplant.
• 2:59
  So that that has been an important point.
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  But we have now learned that biological risk factors may be
• 3:06
  more important and that includes histological subtype.
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  There are a proportion of patients present with blastoid
• 3:15
  or pleomorphic Histology, which is a high risk factor.
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  Also, proliferation is important, EI 67, about 30% is a
• 3:25
  biological risk factor. And perhaps the most important
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  one that has been recognized is the presence of TP53 mutations.
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  It means that the patient will have a very short remission with
• 3:37
  standard chemo immunotherapy. So in first line, what, what is,
• 3:41
  what was the standard of care before in first line and what is
• 3:45
  it today? Yes.
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  So this for as I mentioned younger patients, the standard
• 3:50
  of treatment was alternating and recycling based therapy like our
• 3:55
  CHOP alternating with hydrocytairabin based regimen
• 3:59
  that could be cytairabin only or the HAP and then consolidation
• 4:05
  with Toluca stem cell transplant.
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  We also learned that maintenance with ritaximab prolongs overall
• 4:12
  survival for this subgroup. So that was the standard for
• 4:15
  younger patients. For elderly patients that are
• 4:18
  not eligible for Toluca stem cell transplant, the standard
• 4:22
  has been more lower intense chemotherapy like arbenomastin
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  has been the most frequently used.
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  Our CHOP has been used and also VR cap which is art chop with
• 4:35
  bortisamib instead of being Christine that has been shown to
• 4:38
  improve survival compared to to art chop.
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  But for elder patients, the most common has been Arban, I would
• 4:43
  say. And what is it now?
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  What are the the recommendations in the new guidelines?
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  Yes, for younger patients a major step forward has been the
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  results of the huge European Triangle trial which has been
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  meant paradigm ship 5th in the treatment of of methyl cell
• 5:02
  lymphoma. In this trial, the standard
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  treatment that I mentioned with hydrocydiabine and autologous
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  stem cell transplant was compared to two experimental
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  arms. In one arm, ibrutinib was added
• 5:13
  to our shop in induction and also as maintenance for two
• 5:17
  years. And in the third arm, the second
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  experimental arm ibrutinib was added but autologous stem cell
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  transplant was removed. So and the results show that the
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  addition of ibrutinib to induction and maintenance
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  improves overall survival. We all know that and there is no
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  difference if we use we give autologous stem cell transplant
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  or not. So the standard treatment now is
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  Archop plus ibrutinib alternating with D Hep or D hex
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  which is oxaliplatin instead of synthpatin and then maintenance
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  with ibrutinib and ritaximab. So no more a Tolga stem cell
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  transplant. So that, that is the most
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  important change. So that will definitely reduce
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  toxicity for patients and the efficacy is also much better.
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  So with an improvement in overall survival.
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  So that's the new standard treatment.
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  And this as we remove autologous stem cell transplant, we can
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  give this type of regimen to also patients that are above 65
• 6:19
  years, perhaps around 70 years. So that that's the new treatment
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  for that population. And then the but the majority of
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  patients with mental cell lymphoma, they are elderly.
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  The median age is about 71 years in population based studies, a
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  large proportions will not tolerate this regimen.
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  And they for for that population are still an option, I would
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  say. And VCAP as mentioned, but there
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  has also been studied studies that add ABTK inhibitor to
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  arbenomastin to see if that improves outcome and it has been
• 6:59
  shown to improve progression free survival definitely by
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  adding ibrutinib or acalabrutinib to arbenomastin.
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  So that can also be a standard option for for some patients,
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  but it also increases the toxicity of this regimen.
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  But that's another standard option.
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  And there are also now trials showing that only a BTK drib in
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  combination with the CDT, the CD 20 antibody like
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  ibrutinibritaximab is at least equal in efficacy to
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  urbanaumastin. So that may also be an option
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  for for elderly patients. And how do you choose among all
• 7:40
  these options that are suggested in the guideline?
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  Yes, for younger patients, I think it's easy because we have
• 7:47
  a very good regimen according to the Triangle trial.
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  But for elderly patients, it's it's, it's, it's difficult, I
• 7:53
  think to choose the right treatment because an important
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  study regimen in at relapse is CAR T cell therapy.
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  And we know that benamastin impairs T cell activity, both
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  the number of T cells and the activity of T cells.
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  So in patients that have a high risk of relapse and may need
• 8:14
  cortisol therapy, we'd we'd like to avoid benamastin.
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  Then we look at biological risk factors.
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  So patients without biological risk factors, I would prefer are
• 8:24
  benamastin or are ibrutinib if that is available, if that is
• 8:30
  possible to use or retax combined with another BTK
• 8:33
  inhibitor. But for high risk patients it's
• 8:36
  it's harder. We would like to avoid
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  bendamustin. So in that situation, I think
• 8:41
  the CAP could be an option for elderly patients avoiding
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  Bendamustin. So as you mentioned now there is
• 8:48
  an option of using BTKI in first line in all patients and frayed
• 8:53
  patients. So now that BTK is are moving
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  into first line, what are the recommendations for second line?
• 8:59
  Yes, it depends on on the situation also here because now
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  in the triangle regimen the the there is a specified duration of
• 9:08
  limited duration of of maintenance with BTK inhibitors.
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  So patients who have received ibrutinib for two years
• 9:15
  according to the triangle regimen and stop and then a year
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  after have a relapse, they can be restarted on a BTK inhibitor
• 9:25
  again. So that is one situation perhaps
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  more commonly that the relapse occurs during the treatment with
• 9:31
  the BTK inhibitor and then the disease is refractory to BTK
• 9:36
  inhibitors and we we need something else.
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  And then we have a couple of options.
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  We have CAR T cell, Brexit cell is the one that is approved in
• 9:45
  in Europe. So that is 1 standard option in
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  this situation and the one with perhaps the highest activity as
• 9:51
  well. But we also have now available
• 9:53
  in Europe pertobrutinib which is a non covalent BTK inhibitor
• 9:58
  that has activity also in patients that are refractory to
• 10:02
  to covalent BTK inhibitors. So that that is another option
• 10:07
  and it can also be used as a bridge to to Cartesian treat.
• 10:12
  But there are also other possibilities like chemo,
• 10:16
  immunotherapy, our back for instance, that is retax map,
• 10:20
  venomastin and cytourbin is an option and our Gemox can be an
• 10:24
  option as well. And there are also other agents
• 10:27
  that are under development like other BCL 2 inhibitors and buy
• 10:32
  specific antibodies. So all of these novel therapies
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  are not the same price tag. How widely are they available,
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  especially obviously car T, but some over the others are also
• 10:43
  very expensive. Are they used widely in Europe?
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  Yes, I think they are available in most European countries now.
• 10:50
  Brexit sell but not in every country.
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  But in most countries they are available.
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  They are considered cost of cost effective and are reimbursed,
• 10:59
  but not not everywhere. So this doesn't play a role or a
• 11:04
  big role in choosing which will be the second line, not the
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  price tag. It will be really the clinical
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  situation. Yes, I think in most cases yes.
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  But the problem is that the cortisol therapy in mental cell
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  lymphoma is not curative as it is in diffuse large B cell
• 11:21
  lymphoma. So we don't see a plateau in in
• 11:25
  progression free survival as clearly at least as in as as in
• 11:29
  diffuse large B cell lymphoma. So which other therapies can we
• 11:33
  expect in the future? What is in the pipeline that you
• 11:36
  were referring to? Yes there is.
• 11:38
  For instance, Sondrotoplex that is another BCL 2 inhibitor that
• 11:43
  is active in relapsed mantle cell lymphoma also after BTK eye
• 11:48
  failure and also CD20CD3 bispecific antibodies like
• 11:54
  glofetamab and epcoritamab are very active in in this
• 11:59
  situation. We will also probably see other
• 12:02
  CAR T cell products like Lisa cell is approved in in the US
• 12:07
  for instance for relapsed mantle cell lymphoma and has a lower
• 12:11
  frequency of of the CNS toxicity compared to to Rexocell.
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  It's also an attractive option. So how do you feel this new
• 12:20
  guidelines fit in the daily clinical practice?
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  Well, now I think the the the guidelines are in line with the
• 12:29
  current situation and what is also very positive, I think that
• 12:33
  these can be updated more frequently than that.
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  We hope that these will be updated yearly at least, so we
• 12:39
  don't have to rely on obsolete guidelines that cannot be used.
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  So I think we're in a much better situation now than we
• 12:48
  were before. So is there anything else that
• 12:50
  you would like to add for the audience that I haven't asked?
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  Radiotherapy is also very active treatment in mental cell
• 12:56
  lymphoma. That's that's something we may
• 12:59
  forgot. It's, it's easier for
• 13:01
  oncologists to use radiotherapy perhaps than for hematologists.
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  Mentholine format is extremely sensitive to radiotherapy.
• 13:08
  So that that's a good option also at relapse and also as a
• 13:12
  bridge to to call T cell therapy.
• 13:14
  Another possible treatment is is also allergenic stem cell
• 13:18
  transplant and that was used more frequently before, less
• 13:22
  frequently when we have access to Corti cell therapy.
• 13:26
  Limitation is also age that many patients are elderly with mental
• 13:31
  cell lymphoma. But there are still I think a
• 13:34
  population that may benefit from allotransplant at least after
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  Corti cell therapy. It may be still the only
• 13:44
  curative treatment for mental cell lymphoma, but I think
• 13:47
  Mantasalam foam has not been considered curable.
• 13:50
  But that is something that I think and hope will change that
• 13:54
  this will be a curable disease. I think we will be able to see
• 13:59
  that. With which agents?
• 14:00
  So you say that car T therapy is not doing it so ACT it's an
• 14:05
  option but less use now And what could be a curative option?
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  I think we cure patients already now with the more intensive
• 14:14
  treatment and the triangle regimen I think will be curative
• 14:18
  in a higher proportion of patients.
• 14:21
  That's my hope at least because it's clearly improves overall
• 14:26
  survival. And I think even even with this
• 14:29
  previous standard of treatment, we have seen that after 20
• 14:32
  years, 1/4 of the patients are without relapse and remission.
• 14:37
  They may be cured with a with a new regimen that is more
• 14:41
  effective. I I expect we see an even higher
• 14:45
  proportion that will be have a long term remission.
• 14:47
  Which is excellent use. So if you want the audience to
• 14:50
  remember just one thing from the guidelines or this podcast, what
• 14:53
  would it be? Well, the treatment for at least
• 14:56
  for younger patients with metals and lisinophone has undergone a
• 14:59
  significant change now during the the last couple of years
• 15:04
  that will probably probably have a major impact on on the outcome
• 15:09
  and possibly be a curative treatment for mental health.
• 15:12
  So pay attention to these guidelines and use the new
• 15:15
  treatments and the recommendations that you have
• 15:17
  made. So thank you very much for
• 15:19
  sharing your experience with us. Thank you so much.
• 15:22
  Thank you to the audience for listening and if you enjoyed
• 15:25
  this episode, please like it and subscribe to our channel.
• 15:29
  Stay tuned for more episodes of EHA Unplugged.