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GoCART Coalition (with Prof Christian Chabannon) · EHA Unplugged

• 0:03
  Greetings and welcome to EHA Unplugged, the official podcast
• 0:07
  channel of the European Hematology Association EHA.
• 0:12
  Hello, I am Isabella Rivera, a medical writer for EHA, the
• 0:15
  European Hematology Association. Welcome to this podcast on the
• 0:20
  Go Kart Coalition. Today I have the pleasure to be
• 0:25
  joined by Professor Christian Chabanon.
• 0:28
  Welcome. Could you please start by
• 0:32
  introducing yourself to our audience?
• 0:34
  Yes, Isabel, thank you for having me here.
• 0:38
  I am Christian Chabanel, I am a French hematologist physician
• 0:44
  working in Marseille. I work both at ex Marseille
• 0:49
  University and at the Institute Pauli Kelmet Comprehensive
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  Cancer Centre that hosts a large hematology department, a large
• 1:01
  transplant program and more recently we have onboarded all
• 1:06
  the CAR T cells activities as well with several other programs
• 1:13
  such plan to deliver gene therapies to various categories
• 1:18
  of patients. Thank you for being with us
• 1:21
  today. So to start things off, can you
• 1:24
  please explain what is the go Kart coalition?
• 1:27
  The Go Karti Coalition was created in 2020 during the
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  second European EBMTER CAR T sales meetings that took place
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  in Sigis in Spain. And several individuals
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  including myself working already either with EDMT or with ER
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  foods that we needed a sort of collaborative space where to
• 1:59
  bring the different interested parties around the table and
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  faster exchanges. I think advanced therapies in
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  general, CAR T cells in particular, raise very specific
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  questions, both in terms of development, preclinical and
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  early clinical development, but also in terms of equitable
• 2:25
  access, safe administration that has, I've never been encountered
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  previously with conventional drugs and medicinal products.
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  And this can be solved only if all interested parties work
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  together to again solve this very complex and multifactorial
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  issues. So that was the intention of of
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  Gokarti Coalition to create this open, transparent community and
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  have not only academic representatives, but also
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  representative from the industry, from healthcare
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  organizations at both at the national and European levels and
• 3:13
  most importantly patients, representatives and advocates.
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  So it was founded by EHAIEBMT together.
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  Right. And this was also a very
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  symbolic achievement that two European professional
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  associations came to jointly support a raising initiative.
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  And one of the very important strategic aspects of the Go
• 3:49
  Kartik Coalition was to avoid redundancies.
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  So that was one of the motivations behind the creation
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  of Go Kart Coalition, so that we would take advantage of the
• 4:03
  expertise of those different individuals that primarily work
• 4:08
  with EBMT or primarily work with ER and bring them together.
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  So what are the goals of this coalition?
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  The goal is to is is first of all to help European teams to
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  close the gap with teams in North America and in Asia in
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  terms of of development. Unfortunately, it is fair to say
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  that Europe pretty much missed the early phase of development
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  for immune effective cells based therapy.
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  So Go Kart coalition, one of the objectives is to help European
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  teams to get together. The second aspect is to foster
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  access to this therapies. Through that we hope that we
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  will increase the different levels of access across European
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  countries. And this is one of the main
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  goals. And finally trying to better
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  understand what patients want and need.
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  And you know, doctors are a bit, I would say rudimentary in, in
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  their thinking. We very often measure our
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  success in how do we improve survival.
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  But if you listen to patients, I think patients will tell you
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  that, OK, this is not only a matter of quantities, this is
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  also a matter of quality. So this is also something that
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  the go Kart is trying to to address.
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  So in your website you list five work packages, there is data
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  harmonisation, there is standards of care, education and
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  training, policy and advocacy and scientific excellence.
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  Can we have a quick overview what the activities of Go Kart
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  have been on each of these fields or directions?
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  Can we start first by standards of care?
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  Standards of care again trying to reduce variability across
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  centers in several aspects of medical practice.
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  Areas that have been addressed are one collection of the
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  starting materials that allows to initiate the manufacturing of
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  the medicinal product. So there is a group of experts
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  trying to define what are the best practices in the field in
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  terms of, you know, planning the collection, fine tuning the
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  parameters during collection, maybe predict what is the the
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  quality of the collected cell product and that how it would in
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  turn affect the clinical efficacy of the final product.
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  So this group has already published one paper and is
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  working on the second one. How do pharmacists receive,
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  store, handle for and administer the product to the patients has
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  been the concern for another group of experts and this group
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  also published recommendations and guidelines in our recent
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  manuscript. And this is only for the supply
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  chain. But of course, mitigating the
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  risks of side effects when treating patients is another
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  area where we can contribute to produce and improve guidelines.
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  So. You're trying in general to
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  harmonise practices across countries, across centres, also
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  harmonize centre qualification. Is that also?
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  Yeah, this is correct. The centre qualification process
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  is a very time consuming process that is currently being imposed
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  by all the pharma companies that manufacture car T cells.
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  So pretty much look at your quality management system and
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  they provide some specific education to again mitigate
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  risks, specific risks associated with the administration of CAR T
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  cells. In fact, more than six years
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  after the first market approvals in Europe, all centers and all
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  specialists have come to the conclusion that this pharma
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  specific qualification processes are largely redundant.
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  So the idea is that to alleviate the workload imposed on centers,
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  there could be a core training and a core evaluation that could
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  actually be subcontracted to 1/3 and independent party.
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  And that could be JC which is the EBMT accreditation system in
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  place for more than 25 years now.
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  And that also overviews many of the aspects necessary for CAR T
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  cells that are already in place due to the pre existence of
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  hematopoietic cell transplant programs.
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  So JC may cover the core aspects of the qualification process for
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  centers and then pharma would have to deal only with the
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  specific aspects of their products and their indications.
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  So this could be part of the needs in education and training
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  team Gokakis also. So center qualification mostly
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  reflects a global organization including the quality management
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  system. And on top of that, we believe
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  that different categories of healthcare professionals do need
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  to have some specific training for the management of patients
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  treated with scar T cells. And so this is what we recently
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  designed as a passport initiative, which is sort of a
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  driving license with limited validity in time to actually
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  testifies that one given individual has acquired the
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  minimal essential knowledge that is needed to again ensure
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  patient safety and and and treatment efficacy.
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  And we are working to build this individual passport taking
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  advantage of existing educational initiatives and
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  tools. One of them is the Car T
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  Handbook. The Cartian book was The 1st
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  edition was published a couple of years ago and again, that was
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  an initiative supported both by ER and EBMT.
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  So we are revising and expanding the content of the Cartian
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  books. We have designed it in a purely
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  digitalized format so that revisions can happen more often
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  as needed with the advancing knowledge and the content will
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  be used to design an exam that will allow people to get the
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  passport. Another important aspect in the
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  passport is that it will go beyond training of people at
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  treating centers because we also realize that a critical aspect
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  in access is that the hospitals that cannot directly deliver CAR
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  T cells still need some professionals to have knowledge
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  and expertise in CAR T cell treatments.
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  To identify the right patients at the right time.
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  Absolutely. So in policy and advocacy,
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  there's a regulatory framework called Hospital Exception, A
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  framework from the European Union that allows academic
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  centres and hospitals to develop ATM PS such as Kartis.
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  So we heard in this meeting from Julio Delgado that this hospital
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  exemption is being revised and a bit at risk.
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  What is the Karti Coalition doing about this?
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  Well, the Gogarti Coalition is trying to produce some
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  recommendations to policy makers at the European level to stress
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  and emphasize how important it is that the hospital exemption
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  is maintained in the next version of the pharma regulation
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  and the ATM peer regulation. So maybe for people who are not
• 13:19
  aficionados of the regulation, I need to explain a little bit.
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  When advanced therapies are made or manufactured from sales, they
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  are manufacturing process borrows both from the practice
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  in cell transplants and from more or less sophisticated
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  biotechnological processes. But this biotechnological
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  processes results in significant changes in the functions of the
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  collected cells. And this is where the frontier
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  is between cell transplant and medicinal products.
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  But historically, in Europe and across the world, medicinal
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  products are manufactured by the industry and intended to be
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  placed on the market. So once the original version of
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  the regulation, the European Regulation and Advanced Therapy
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  Medicinal Products was released in 2007, that meant that some of
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  the therapeutic products that were previously produced and
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  distributed by tissue establishments were then
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  classified as medicinal products.
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  And then the consequence was that they had to be manufactured
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  by pharma companies. And for some of those products
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  pharma company have no interest because they consider there is
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  such tiny market. So the first version of the
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  regulation contain the provisions that was called the
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  hospital exemption, allowing some tissue establishment,
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  academic infrastructures, small private infrastructures to
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  manufacture some batches of advanced therapies such as car T
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  cells to cover these needs for orphan situations.
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  So there are huge differences in the way that the different
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  countries implement the hospital exemption.
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  You mentioned Spain, where there has been a remarkable project
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  and work carried out to make CAR T cells available to a fraction
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  of Spanish patients taking advantage of the hospital
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  exemption. I am French and living in a
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  country where the policy is totally opposite.
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  Our competent authority is very reluctant to allowing academic
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  infrastructures to produce some small batches.
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  But obviously we have a problem because the implementation of
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  the hospital exemption is quite heterogeneous across across
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  countries. And this is one of the reasons
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  why it's being discussed currently at the at the European
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  level because the pharma regulation and the ATMP
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  regulation again are in the process of being revised.
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  We do believe as EBMT, as Go Karti Coalition and I believe as
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  EHA, we do believe that it should be maintained in the next
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  version. But that's ongoing discussions.
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  And so again, to come back to your original point, what we
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  have realized over time is that academia needs to have its voice
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  listened to by policy makers, especially at the European
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  levels, and we need to get organized to have people who can
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  go to the European Commission on a regular basis, who can answer
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  surveys, who can answer public consultations.
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  Finally, there is also data harmonisation.
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  There has been a registry created by EBMT and is
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  collecting data from all patients that receive car T How
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  was this registry set up? What kind of data is it
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  collecting? Yeah, data actually maybe is the
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  most important aspect because we need data to run proper analysis
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  and support relevant decisions for all the aspects that we
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  previously discussed. The EBMT registry has collected
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  over time information on more than 700,000 patients who
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  underwent hematopoietic cell transplant and more than 800,000
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  transplant because some patients do receive multiple transplants.
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  Based on this experience, in the mid 2010, we expanded the
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  capacity of the EBMT registry to capture data not only on
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  transplant patients but now on patients treated with scar T
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  cells. TMA published positive opinion
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  on the cellular therapy module to register patients treated
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  with scar T cells and collect data and follow up.
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  We now have more than 12,000 patients registered with the
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  EBMT registry and we have more or less limited follow up on
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  these on these patients and it's growing.
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  On top of that, we have contracted with some of the main
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  car T sales manufacturers to run what we call BASS Post
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  authorization safety survey. And these are intended to
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  capture information with highest granularity in order to be able
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  to detect signals for unpredicted or unpredictable
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  toxicities or side effects in real world condition.
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  And we've been publishing the 1st results of large courts of
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  patients included in this past studies.
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  But then during this 66 year process, we realized that again
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  there were many interested parties in the field and that
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  each of these interested parties had different interests.
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  So we need to move on and and and enrich the party sales
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  registry by adding information. Or maybe a refining already
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  included information. Recently we've used methodology
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  which is called Delphi, Delphi survey.
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  And so we asked people what kind of information is important to
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  them and in which format basically.
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  And we had a meeting with another European initiative that
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  is called T2 Evolve. And what was somewhat surprising
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  was that actually there is only a minority of information for
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  which there is a consensus. So maybe also that suggests that
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  we may not be aiming at collecting a huge amount of
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  information, but but possibly only a limited number of
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  information, but of high quality.
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  Or maybe we could collect information with a very high
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  definition, if I can say only on samples of patients.
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  Ironically, I commented that we closed the loop and came back
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  because that has been the design of the BMT registry for many
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  years now. But at least we have a
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  scientific approach there to build a consensus.
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  So we try to promote use and reuse.
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  We believe that analysing data sets also results in improving
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  the quality of the data because you obviously double check and
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  you identify inconsistencies or errors.
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  So we are really try to promote and this is the goal of the
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  scientific excellence work package where we have launched a
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  call of interest for the last four years and selected now 11
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  projects, three this year in 2024.
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  So one key objective of Go Kart is really you know to open the
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  door to new users. This is a complex landscape
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  because the EBMT registry basically used to be the only
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  registry for hematopoietic cell transplantation in Europe.
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  And the situation for quality sales is very different because
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  that has generated interest from many more communities.
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  So how do we try not to duplicate again efforts and
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  money and energy? And this is something we are
• 22:30
  working at at Workhart. So to be naive, if you're an
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  investigator and you want to access this data to work with
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  this data, how do you do it? Well, it's quite simple because
• 22:44
  there is a, a, a door to enter the EMT registry and you can
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  contact people there and, and also there will be another call
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  in 2025 for, for Go karts. There are two coordinators for
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  the Go Karty Coalition who are ready to answer any sort of
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  questions in relation to Go Karty activities.
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  So there is no need to have funding from a go Kart to access
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  this data so you can have your own funding.
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  Yeah, you can have your own funding and again, you are quite
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  open and flexible in terms of, of, of giving access in the
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  process of, of scientific excellence.
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  There is a, a reviewing process in place of course.
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  But otherwise, we are very happy that people outside of BBMT I
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  can use the the data in the registry and and bring new ideas
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  and new initiatives. Do you have any example of a
• 23:48
  project that has been possible because of this EBMT registry?
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  There are 11 projects that are that are carried under the
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  auspice of the Go Karty Coalition.
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  One of the phrase that we selected was the use of CAR T
• 24:08
  cells in patients who have also received solid organ
• 24:13
  transplants. We've looked at the influence of
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  in food depletion as an example on the outcome of CAR T cells.
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  But we still have a number of questions.
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  We are digging always deeper to further understand what are the
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  determinants of success when treating patients with CAR T
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  cells and also adjusting the use of CAR T cells to an ever
• 24:40
  changing world. The therapeutic landscape in,
• 24:44
  in, in the, in, in the diseases that we treat with CAR T cells,
• 24:49
  that's a lymphoma, myeloma Cape is ever expanding with always
• 24:53
  more options. We've seen that with the
• 24:57
  introductions of what we call B specific antibodies.
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  So one of the questions, no one has the answer which order
• 25:06
  should we use those products, Should we use them sequentially
• 25:10
  simultaneously? Should we use one to bridge to
• 25:13
  the other. So many of these questions will
• 25:16
  be addressed through the use of registries and again, will need
• 25:23
  the contribution of more individuals coming from
• 25:28
  different organizations. So how do you see the future of
• 25:38
  a go Kart? One of again one of the big
• 25:42
  projects is to have this passport ready to use.
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  At the same time, we will keep promoting the use and reuse of
• 25:52
  the data in order to better understand what is at stake when
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  treating patients with scar T cells and other form of immune
• 26:00
  cell therapies. And also we need to address the
• 26:05
  consequences of these therapies. Moving outside of hematology to
• 26:10
  different fields, there is a lot of excitement and using CAR T
• 26:17
  cells for autoimmune diseases as an example, lot of hope and
• 26:22
  excitement in the field that needs to be confirmed in real
• 26:26
  world conditions. And yes, these patients will
• 26:30
  need to be registered. I we believe the EBMT registry
• 26:34
  may be a suitable tool to register these patients.
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  EBMT has created an autoimmune disease working party for many
• 26:42
  years before because before CAR T cells, we are using as an
• 26:46
  example autologous hematopoietic cell transplantation to treat
• 26:50
  some patients affected with autoimmune diseases or chronic
• 26:54
  inflammatory disorder. Most of the expertise is outside
• 26:57
  of ER and outside of EBMT. So we'll work on bridging
• 27:03
  between these different communities.
• 27:06
  So the limits of the work for this coalition, especially for
• 27:12
  the registry, are ever expanding.
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  The work is not done. No, the work is not done because
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  we are living in a changing environment.
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  So even if we were happy to claim today that we have met
• 27:24
  100% of our original objectives, which which obviously is not
• 27:28
  true, is there would be new objectives because again, the
• 27:32
  field is expanding. It's very hard to predict
• 27:38
  where's the actual and impacting changes will take place.
• 27:46
  We also expect future progress in the field of solid tumors
• 27:51
  where there are many unmet needs.
• 27:54
  You may have heard of the original and encouraging success
• 27:59
  in the field of glioblastoma for example, or in children,
• 28:03
  neuroblastoma, meduloblastoma and so on.
• 28:06
  Trying to anticipate what would be the consequences, let's say
• 28:10
  if a CAR T cells could be used to treat patients with frequent
• 28:17
  forms of solid tumors, let's say colon cancer for example or lung
• 28:25
  cancer. And again, Go Kart will be there
• 28:28
  to contribute to this advances. Is there anything else you would
• 28:36
  like to say to the audience? What would be your take away
• 28:39
  message? Well, my take away message is
• 28:42
  again, Go Kart is a community and you're welcome to join the
• 28:46
  communities. So biomarker, if I can say so,
• 28:51
  if I was success would be to have more organizations and more
• 28:56
  individuals affiliated with, with Go Kart.
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  And from a more personal viewpoint, I was one of the the
• 29:07
  individuals who originally thought that was something
• 29:11
  useful to the community. And I would be delighted to have
• 29:15
  all junior people join the join the community and join the the
• 29:20
  initiative. Well, thank you very much,
• 29:24
  Professor Shabano, for this insightful conversation and for
• 29:30
  sharing all your experience with us.
• 29:34
  Thank you to all of you for listening and stay tuned for our
• 29:38
  next episode.