Latest / EHA Unplugged / First-line Treatment of Primary Central Nervous System Lymphoma (PCNSL) (EHA2024)

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First-line Treatment of Primary Central Nervous System Lymphoma (PCNSL) (EHA2024) · EHA Unplugged

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  In this episode of EH Unplugged, we will revisit a spotlight talk
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  from EHA 2024. Doctor Elizabeth Schorb from the
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  University Medical Center in Freiburg presents on the first
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  line treatment of primary central nervous system lymphoma,
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  which has seen tremendous advances in the last years.
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  My aim is to share with you my excitement about the first line
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  treatment of primary central nervous system lymphoma and
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  share them experience that might be inspiring and helpful for for
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  you whether in PCNSL or even in other diseases.
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  There have really been tremendous advances in the first
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  line treatment of primary central nervous system lymphoma
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  during the past years. But of course, all of you know,
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  there's been a lot of data, a lot of clinical research behind
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  it. It's been it's been a real
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  fireworks display. And my aim is to get to the
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  heart of this great story in just about the next 15 minutes.
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  As you will hear in my talk, all of these advances would not have
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  been possible without international collaborations.
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  And that is that is why I'm so pleased to stand here at this
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  stage and share this story with all of you.
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  From my point of view, PCNSL is really a special disease.
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  This is mainly due to the cost that it is not a disease you
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  would have to deal with on a daily basis.
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  The incidence is quite low. So by definition, it is a rare
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  disease, but it's also a special disease because of its location.
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  Time is brain The central nervous system does not allow
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  treatment or delay and therefore requires multidisciplinary and
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  prompt action. And that means that the making
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  the diagnosis promptly and starting treating the treatment
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  quickly is very important. So, but when we get to the point
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  of starting treatment, everything we have learned about
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  treating systemic aggressive lymphomas in our careers does
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  not really apply for PCNSL patients.
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  There are barriers to overcome. The blood brain barrier rejects
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  the treatment we know from treating systemic aggressive
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  lymphomas such as our CHOP for example.
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  This makes them an inadequate treatment options for our PCNSL
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  patients. And it's precisely because of
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  the rarity of the disease and its special challenges that all
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  the impressive advances that have been done in the field of
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  primary central nervous system lymphoma have only been achieved
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  by thinking outside the box by driving forward investigator
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  initiated clinical research. Even though the rarity of the
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  disease made patient recruitment even more difficult, and
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  conversely, the pharmaceutical industry's interest in testing
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  new drugs lower than in many other hematological diseases,
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  When I started to look at primary central nervous system
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  lymphoma about 15 years ago, the knowledge of treatment options
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  was still very limited. Data was scarce because of the
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  rarity and the nature of the disease, which made it difficult
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  to conduct clinical trials and to generate evidence.
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  At that time, despite many attempts to change the
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  situation, our job was still the benchmark for first line
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  treatment of systemic aggressive lymphomas and would remain so
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  for many, many years. A similar picture has emerged
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  with regards to the treatment of other brain tumors such as
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  gliomas for example, where unfortunately very little
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  progress has been made during the past years despite a large
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  number of patients. In contrast, the treatment of
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  PCNR cell has really exploded during the past 15 to 20 years.
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  Fortunately, when I completed my studies, I met a group of really
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  inspiring people who were working on this rare disease,
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  who were thinking outside the box and who had the courage to
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  take a path that was known from other diseases but was
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  completely unknown in the context of treating brain
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  tumors. And these group of people
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  completely reinterpreted the treatment principle of treatment
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  intensification in terms of the blood brain barrier.
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  And I saw how difficult this path could be at a time when
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  clinical research was still struggling at many places.
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  But they remained motivated and passionate about clinical
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  research in primary central nervous system lymphoma.
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  And I'm so grateful that they captured me with their
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  enthusiasm and their motivation and that I became a part of this
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  wonderful international study group at the very beginning of
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  my hematological career. Then 45 year old patient
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  symbolized this motivation. He was diagnosed with PCNR cell
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  in 27 and was treated with hydrochemotherapy and autologous
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  stem cell transplant within the CNSNHL trial.
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  This patient was young and athletic and his biggest wish
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  was to be able to lace up his running shoes and go jogging and
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  compete as soon as possible after treatment.
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  And I watched as his disease went into this into complete
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  remission and just a few months after stopping hydrocemia
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  therapy and autologous stem cell transplant, he would lie, lace
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  up his running shoes, go to the starting line and ran 1/2
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  marathon. He had his old life and his
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  dreams back, and I could really understand his joy.
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  And it was in that moment that I realized that I was just at the
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  right place and I really wanted to have more and more PCNSL
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  patients to get better and better treatment options.
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  And that motivation has slapped me on an incredibly interesting
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  journey that I would now like to share with you.
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  The treatment of PCNSL today is based on two pillars As for
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  other hematological diseases as well induction treatment as well
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  as consolidation treatment. In contrast to the first line
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  treatment of systemic aggressive lymphomas, an incredible amount
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  has happened during the past years.
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  A disease that is fatal within a short period of time if left
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  untreated has become a curable disease.
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  After the CNSNHL trial, which I've mentioned earlier and from
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  which my first PCNSL patient benefited so greatly, I was able
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  to see first hand how international collaboration has
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  enabled further progress to be made in the treatment of this
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  disease, gradually improving standard of care and that's the
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  prognosis for our patients. I was able to enroll patients in
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  the LSG 32 trial which investigated an intensive
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  induction treatment comprising methotrexate side arabin,
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  rituximab, entire taper and established the so-called matrix
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  regimen as standard induction treatment in many, many
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  countries around the same town. We had the honour of publishing
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  the results of the CNSNHL trial, which would also revolutionize
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  consolidation treatment in the years that followed.
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  The results of this trial confirm my subjective impression
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  that intensification of treatment with high dose
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  hemotherapy and autologous stem cell transplant could really
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  produce excellent long term outcomes and a substantial
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  chance for a cure. A major milestone in the history
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  of PCNSL treatment. A disease that was rapidly fatal
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  if left untreated was transformed into a disease with
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  a long term overall survival of nearly 80% after five years for
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  illigible patients. This sets the stage for further
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  development in Europe and beyond.
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  Subsequently, 2 randomized phase two trials, namely the ILIS G32
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  and the French CRISIS trial, compared myeloablative
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  consolidation with the former treatment standard of
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  consolidating whole brain radiotherapy.
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  As a result of the trial findings, whole brain
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  radiotherapy became less important in weighing the risk
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  benefit assessment of each treatment modality and this was
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  mainly due to the fact that the long term consequences of whole
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  brain radiotherapy in terms of neurotoxicity became more
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  important as the survival of our patients improved.
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  Consequently, consolidating whole brain radiotherapy is now
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  only reserved for specific cases, and all these
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  developments have only been possible by pooling European
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  forces. My view of these European
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  collaborations was sharpened by an incredibly educational time
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  on the EH as clinical research training in the Hematology
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  program, where I met inspiring people and gained important
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  insights into the clinical research landscape.
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  I am incredibly grateful to have had this experience, experiences
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  that have shaped me to this day. Based on this scientific and
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  personal experience, I was able to participate in the world's
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  largest randomized phase three trial to further investigate
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  consolidation treatment, the Matrix trial.
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  I have learned not only how important supportive care and
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  physician experience are in addition to effective
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  combination treatment, but also how exciting international
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  collaboration can be. In particular, the MATRIX trial
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  looked at whether high dose hemotherapy and autological stem
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  cell transplant as consolidation was really necessary or whether
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  even non myeloblative approaches could produce similar or even
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  better results. The result of this trial is
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  really a milestone in PCNS cell treatment, not only because this
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  study can be considered a real successful European
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  collaboration in a rare disease, but also it it achieved
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  something that had not been seen for years in the treatment of
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  systemic aggressive lymphomas or in other brain tumors for
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  decades. A clear advantage not only in
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  terms of progression free, but also in overall survival for
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  those patients who were treated with hydrochemotherapy and
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  cancer and autological stem cell transplant.
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  And this late breaking use was presented at their annual
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  meeting in 2022 and will be fully published shortly.
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  And so many people have benefited.
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  But the marathon runner I told you before was young, athletic
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  and fit. And as you can imagine, not all
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  PCNS, our patients, meet these criteria.
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  And over the course of my career, I've been particularly
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  motivated to bring promising treatment options to these
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  people as well. Recent and ongoing studies have
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  aimed to make highly effective, effective therapeutic approaches
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  available to a larger group of patients.
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  The recently published phase two Marta trial investigated or
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  showed that a short induction with rituximab site, site arabin
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  and methotrexate followed by H adapter titles, humotherapy and
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  autological stem cell transplant was visible and effective even
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  in patients above 65 years of age.
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  We have also learned that the very early phase of treatment is
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  crucial because we do still lose many patients there.
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  This is the basis for ongoing studies with the aim to minimise
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  early toxicity like in the European Optimate trial, and
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  International Studies are also investigating how the addition
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  of novel targeted agents can further improve induction
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  treatment. In addition, it will be very
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  interesting to learn how novel biomarkers and therapeutic
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  approaches like CAR, T cell therapy or even bispecifics in
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  the future will further shape first line or further treatment
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  of PCNSL patients. And from my point of view, it
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  speaks volumes that this disease with data on circulating tumor
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  DNA in PSPCNSL made it even to the plenary stage of the ASH
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  meeting in 2021, where this rare disease was heard on this great
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  hematological stage. Inspired by my experience over
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  the past 15 years, I have witnessed a veritable firework
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  display of PCNSL development. I am very positive and
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  incredibly excited about everything that awaits us in the
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  upcoming years. As you can see, we do see things
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  different now and we have gone places we couldn't have dreamed
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  of before. I could never have imagined that
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  I would be standing here today at this stage reporting on these
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  great advances in the field of primary central nervous system
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  lymphoma. And what's 15 years in clinical
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  research? It's really a short amount of
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  time and that is why I'm standing here today.
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  And with this experience, I have no doubt that in the 15 years
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  time we will be able to reach even different heights.
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  And that's what I do hope for in the future, not only for PCNSL,
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  but for other diseases as well. I hope I have passed on you some
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  of my enthusiasm, and I will be delighted if you take away with
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  you the idea that it is possible to break barriers and seek out
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  the great challenges. It is important to remain
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  curious and ambitious to be cooperative and collaborative.
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  After all, interacting with people and colleagues make us
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  better clinician scientists and clinicians, even if it can
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  sometimes be difficult. Stay tuned, stay in touch
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  because your investigator initiated ideas can make all the
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  difference and I would like to thank you for listening and
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  thank all of those people who just joined me on this
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  incredibly interesting journey. If.
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  You have a patient where you're in doubt about the fitness of
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  the patients beforehand of the treatment.
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  Would you choose for a more intensive induction treatment,
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  or would you choose for a less intensive induction treatment
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  with all aims to get to a consolidation phase of your
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  treatment? Well, when we're talking about
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  consolidating intensive treatment with hydroshumotherapy
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  and autologous sensor transplant, I'm really convinced
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  of the fact that we that's, that is we should aim to go for.
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  So I would be more likely to just reduce the a little bit of
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  intensity of induction treatment to really read Chido's
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  chemotherapy because we know this component is really
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  important. I would probably do a kind of a
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  preface with rituximab and methotrexate, just have an idea
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  how the patient is, how everything is working out, and
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  then decide if I can add for example side Arab in or maybe I
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  will go on with the MTX ritoxima protocol for the further steps.
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  That's how I'm approaching these situations.
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  What is your strategy for elderly patients who could not
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  be treated by Otologus stem cell?
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  We really still need a lot of more data on it because it's not
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  that satisfactory at the moment. Well, we, we do have a phase
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  three trial where we are comparing the RMP protocol from
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  the pre main study with an intensified regimen.
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  So we would go at the moment we would go for pre main for RMP.
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  But of course we we would be very delighted to add other
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  drugs. We do have another trial adding
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  Lenalidomide and tafacetamab, just a little phase two trial.
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  I'd like to know what is your strategy for the patients who
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  relapsed early relapse after intensity treatment with auto
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  transplantation? Yeah.
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  Well, speaking about early relapses, I think the CAR T cell
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  approach is quite promising. We do have a certain amount of
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  time after high dose hemotherapy.
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  So we would go even for another autologous approach as well.
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  And we did see really brilliant cases.
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  So, but if it's an early relapse, I would really go for
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  car T cell therapy if available. Thank you.