Latest / EHA Unplugged / Thrombotic thrombocytopenic purpura (TTP): Is plasmapheresis history?

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Thrombotic thrombocytopenic purpura (TTP): Is plasmapheresis history? · EHA Unplugged

• 0:07
  Greetings and welcome to EHA Unplugged, the official podcast
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  channel of the European Hematology Association EHA.
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  I'm Elena Relightly from Thessaloniki, Greece.
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  It's a great honor to chair this debate.
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  We have with us today two world known experts in the field of
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  TTP and I would like to give them the chance to ask the
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  question if Plasmaphoresis is history or not.
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  And 1st I would like to introduce to Marie Scali who
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  will try to support that Plasmaphoresis history.
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  Thank you very much. Yes, my brief is to try and
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  convince you that plasmapheresis is going to be history in the
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  treatment of acute TTP. And the reason for this is
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  multifold plasma exchange was first documented in journals in
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  1977. So it's over 45 years that we've
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  been using the same therapy in patients with acute TTP and that
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  involves large amounts of blood product, so plasma, some of
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  which is specially treated, but other therapies in some
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  countries not so. And with that brings the risk of
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  pathogen transfer, it brings the risk of anaphylaxis.
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  It requires specialist units, specialist staff to undertake
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  this type of therapy. Moreover, we have to put in
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  large central lines for it to continue day upon day upon day
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  until the platelet count normalises.
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  But not just that remains normal.
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  In 2019, there were two important papers published.
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  The first was the Hercules study and that had been the result of
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  almost 10 years of investigation of this use of this special
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  treatment, which binds to the position of the vilibrant factor
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  that platelets normally bind to. Now why is that important?
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  Firstly, the platelet count normalized much quicker,
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  Secondly prevented ongoing small blood clots that we would
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  normally see associated with end organ damage.
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  But thirdly, it made us realise actually in the past patients
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  continue to die despite the use of plasma exchange and the
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  impact of plasma exchange with immunosuppression hadn't really
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  changed since the mid 1980s. Now with the use of capacizumab
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  on the clinical diagnosis of acute TTP or with confirmation
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  of severe add-ons 30 deficiency, if this can be turned around
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  quickly, we are not seeing the acute deaths, we are not seeing
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  exacerbations and refractory disease.
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  One year ago in 2023, I was very privileged to be able to present
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  in an oral communication the results of using the covenant
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  ATOMS 13 in conjunction with plasma exchange in acute TTP.
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  This was in three cohorts. SO1 cohort just had plasma
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  exchange and placebo and the other two cohorts had
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  recombinant ATOMS 13. And what we saw from this data
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  will be it not in large patient numbers.
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  In placebo, we see the increment in Adams 13 and then drop down
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  the following day, often to less than than 5%, but the increment
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  was not comparable to the use of the recombinant Adams 13.
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  Now clearly more trials need to be undertaken and need to be
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  completed and it needs to go through regulatory approval.
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  However, I'm confident that we will get into a space where we
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  do not need to use three litres of a blood product over many
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  hours where we will achieve lesser benefit compared to using
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  10 mils of the combinent Addams 13, which will produce not only
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  comparable results but likely better results.
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  So in summary, I think our future is using a non plasma
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  exchange approach incorporating recombinant adapt 13,
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  kaplacismab and immunosuppression primarily with
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  steroids and anti CD 20 therapy. Thank you for your attention.
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  Thank you so much, Doctor Scali, for this comprehensive review of
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  the current landscape of TTP. I'm also good to hear the Other
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  Side of the coin by Doctor Koppel, who is going to persuade
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  us that plasmaphoresis is not history yet.
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  Yes. Thank you.
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  So indeed, I'm convinced that in the forthcoming years, test
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  makes change will become history.
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  But for now, I'm also convinced that we cannot offer this text
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  free strategy to all patients with ITTP regardless of clinical
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  presentation and celebrity, simply because we do not have so
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  many data in the use of this strategy in ITTP patients.
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  So far we have one single study that reports search experience
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  besides clinical case reports. This study is online on blood
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  since 2 weeks ago only and it reports only 42 patients treated
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  with a PIX 3 strategy. This is a nice work that stems
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  from very serious and experienced teams, but
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  nevertheless the number of patients reported is quite
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  small, 42, and these patients may not completely represent the
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  world spectrum of ITTP severity, so we must be wise towards the
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  mistakes this work. So 40% of these patients were
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  patients with a relapse of the TTP.
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  So this means that those patients had a known past
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  history of TTP, so they had an anticipable CV here at absolute
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  deficiency and these patients are typically tightly have a
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  tight follow up. So I would say that the
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  diagnosis was likely made more rapidly and more easy.
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  So all this to say that we still have a few experience in the
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  management of patients, especially the most of the cases
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  with a big screen strategy. This is the first point.
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  The second point is that we definitely need some
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  prerequisites before treating all patients with a big three
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  strategy, because first you need to get experience in the
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  diagnosis of patients with TTP. So this means that you have to
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  be familiar with the clinical schools, with the assessment of
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  the severity of the patients with TTP and you need to have a
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  lab that provides you Adams activity in a rapid turn around
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  time so that you make the dynasty of TTP versus the
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  dynasty of other Tmas rapidly. And it's not so easy for every
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  team in the world. You need to have campuses, you
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  have have a label within minutes to kill the patients rapidly as
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  soon as the diagnosis is made or as soon as the patient is
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  admitted. Because if you don't have Kepler
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  or either recommended absurdity and there's no debate.
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  And you also have to have a perfect coordination between all
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  the protagonists involved in the management of patients,
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  including the pharma. And lastly, and this is more a a
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  prospective, I deeply believe that plasma should resist by
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  itself. So I mean the the removal of
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  plasma from the patients is almost history now because
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  clearly it has never been demonstrated that the removal of
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  plasma in these patients allows improving the condition.
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  Some claim that plasma removal allow to remove antibodies
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  against some statin, VWF multimers, some cytokines, some
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  humors from the patients, but this has never been clearly
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  demonstrated. And plasma exchange works in
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  ITTP because it allows to make space these patients to provide
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  plasma and thereby exogenous adamcetin.
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  So now at the time we have the recommend for Adamcetin, it's
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  likely that in this patient, especially in the mostly
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  patients if you want to supply Adamcetin in these patients, you
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  will just have to to provide them recommendant adamcetin.
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  So I'm convinced that plasma pharmacies will disappear in the
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  landscape of IDTP treatment. So in summary, my message is
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  that yes, we are moving to a best free strategy in ITTP
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  patients. But for now if tomorrow you have
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  to manage a patient with ITTP, keep in mind that we need a step
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  by step procedure so that we are safe.
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  It's likely that the most experienced teams will have
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  first to experience this strategy and this is important
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  to avoid and say spoiling the party in the success of the
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  improvement of ITTP problem system.
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  Thank you. Thank you so much, Doctor Kopo.
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  And so a couple of questions. First, Doctor Scali, we heard a
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  lot about the severe, very severe cases.
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  Do you have a comment on the based on all your experience in
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  the field or how can we define these patients?
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  It's obviously a very acute situation when patients come in
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  and so we need to keep it simple.
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  The two parameters that we use really are a troponin level
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  above the normal range and AGCS score, Glasgow Coma Scale,
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  anything below 15 / 15 and that tells us that the patients are
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  severe and may continue to deteriorate.
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  They're simple tests that we can get back quickly and can be done
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  at the right. Side thank you so much.
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  That's a very clear answer. And another question since the
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  field is constantly changing is how do you monitor TTP patients
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  and if you think that this will also affect the future.
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  And a second part of it would be, do you think that they need
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  to be treated and monitor in specialized service at least for
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  this new step wise approach? Yes, this is the point because
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  of the management of ITT patients is hyper specialized,
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  especially if we consider to manage these patients without
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  PEX. And This is why I I was
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  emphasizing that firstly PEX free regiments should be
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  performed by experienced team trained in the rapid diagnosis
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  of TTP versus all the forms of TMA or can have a rapidly
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  capacizumab available or soon recombinant Adam 13 and who are
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  able to manage these patients tightly typically in intensive
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  care units. So there is a sum of many
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  factors that need to be present so that the space free strategy
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  will be a success. Thank you so much both for this
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  great debate that I hope we reach to an agreement at the
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  end. So please closing statements
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  from Doctor Scali. I think we are on the same page
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  even though we are opposite sides in the debate.
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  We can't not use plasma exchange at the moment.
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  But will it be history? I very much hope so.
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  We have to move away from blood products treating this acute
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  condition and use non blood related therapies.
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  ACT. Yes.
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  And indeed we all have the the hope to see the the
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  disappearance of at least plasma cell resist from the therapeutic
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  landscape of these patients. We just have to keep in mind
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  that with the current treatment for these patients, plasma
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  exchange, immunosuppression and capacizumab, we can reach up to
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  99% of survival. So this is a challenging result
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  and it will be challenging to do better with a decrease in the
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  burden of care. So let's go step by step in the
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  in the new procedures. So we have written agreement, I
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  think that plasmapheresis will be history eventually and TTP
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  and maybe we have the advantage to focus on long term follow up
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  of these patients. So I want.
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  Now a second question would be, what is your opinion on the
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  course of current treatment in CTP?
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  It's a very important question. CTP care is expensive
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  regardless. Think you're alluding to the
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  cost of capitalism, which in some countries has resulted in
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  clinicians not using therapy. As clinicians, it's not our job
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  to dictate past. Our job is to ensure that the
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  treatment is effective and safe for patients, of which
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  capitalism is in both situations under specialist oversight.
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  So would and do we use it in the UK?
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  We use it up front on confirmation of an uncertain
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  deficiency, but that's because we have a network nationally
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  that authorises that behaviour. We shouldn't be using it in the
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  refractory scenario. You've missed the boat and we
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  don't know how patients deteriorate, but we should not
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  be commenting on how much or little a therapy costs.
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  Yes. The other point is that we have
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  some room to decrease the global cost of TTP management.
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  First, we are now very efficient in the prevention of relapses
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  and this will modify the studies about cost effectiveness of the
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  management of these patients. Second point is that works are
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  ongoing to better optimize the immunosuppression in these
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  patients to shorten as far as we can the duration of treatment
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  with capacitor. So we are talking about text
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  free regimens. So this means for the patient
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  decrease, substantial decrease in the burden of care and this
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  has to be put forward absolutely.
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  So thank you, Doctor Gabrielati, Professor Scully, and Professor
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  Coco for this facility debate and for sharing your expertise
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  with us. And thank you to all of you for
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  shooting and listening.