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CAR-T Therapy in Haematological Malignancy: Early Stage Outlook [2019]

Product Code:
596201303
Publication Date:
July 2019
Format:
PDF + PPTX
Price:
€9095

Where next for CAR-T therapy in haematological malignancies

Novartis' Kymriah and Kite/Gilead's Yescarta have dramatically impacted treatment outcomes in relapsed/refractory ALL and NHL. In this report, KOLs weigh in on the prospects for an expansion of CAR-T therapy in ALL and lymphoma, as well as into other malignancies. Among the multitude of CAR-T therapies in development for multiple myeloma, which approaches stand out and is BCMA the most promising target? Could CAR-T cells targeting NK cell antigens, e.g. Celyad's CYAD-01 or Cellectis' UCART123, offer hope for AML? CD19-negative relapse remains a challenge and the experts assess the prospects for a dual CD19/CD22 targeting therapy, e.g. Autolus' AUTO3, to mitigate this issue. Furthermore, expert commentary navigates through the myriad of next-generation approaches, including allogeneic therapies and the incorporation of multiple co-stimulatory domains and safety switches.

Eight of the world's foremost KOLs from the US and EU offer candid insights on 2 marketed therapies and 12 pipeline drugs.

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Top takeaways

  • Novartis' Kymriah and Kite/Gilead's Yescarta made headlines in becoming the first CAR-T therapies to be approved. How have they impacted the treatment of ALL and NHL and how will their use in these malignancies evolve?
  • A multitude of CAR-T therapies are in development for the treatment of multiple myeloma. Which approaches stand out and does BCMA remain the most promising target?
  • Celgene's anti-CD19 CAR-T therapy JCAR017 is in development for the treatment of lymphoma and CLL. How does it compare with other anti-CD19 CAR-T therapies and how will it fit into the increasingly crowded CLL treatment landscape?
  • The development of CAR-T therapy for AML is still in its infancy and the identification of an optimal target antigen is an ongoing challenge. Despite these issues, however, which settings and pipeline candidates could offer promise?
  • The availability of an allogeneic CAR-T therapy, such as Cellectis' UCART123, offers promise of a faster turnaround and reduced logistical burden. But how do KOLs think they will compare with autologous therapies in terms of efficacy and safety, and where could they fit in?
  • CD19-negative relapse is a significant challenge, particularly in ALL. Could a dual targeting CAR-T therapy such as Autolus' AUTO3, which targets both CD19 and CD22, help mitigate this issue?
  • A multitude of next-generation approaches to CAR-T therapy are in development, such as incorporating multiple co-stimulatory domains or a conditional safety switch. How do KOLs rate the potential for these approaches to impact the treatment of haematological cancers?
  • What are the key commercial opportunities and challenges for CAR-T therapy in the treatment of haematological malignancies? How could they impact the relative success of these therapies?
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Quotes

"The CD19-targeting therapies for ALL are just the first iteration. If companies are making a decent profit from this, there will be next-generation CARs which target multiple antigens, where the manufacturing is altered so that they have better persistence etc., and potentially incorporating checkpoint blockades."
EU Key Opinion Leader

"It's obviously very attractive to be able to have an off-the-shelf product, and that will drive the cost down, making it much more applicable, and you could use it for larger numbers of patients."
EU Key Opinion Leader

"The CD19 CARs are likely to be curative for at least some patients with leukaemia and with lymphoma. The fact that there are so many sustained remissions going on for years now, I do believe that we can use the word cure."
US Key Opinion Leader

Sample of therapies covered

Marketed Therapies

  • Kymriah (tisagenlecleucel; Novartis)
  • Yescarta (axicabtagene ciloleucel; Kite/Gilead)
  • JCAR017 (lisocabtagene maraleucel; Celgene)
  • bb2121 (Bluebird Bio/Celgene)

Phase I/II Therapies

  • bb21217 (Bluebird Bio/Celgene)
  • JNJ-68284528 (LCAR-B38M; Legend/Janssen)
  • P-BCMA-101 (Poseida)
  • CYAD 01 (Celyad)
  • AUTO1 (Autolus)
  • AUTO2 (Autolus)
  • AUTO3 (Autolus)
  • UCART19 (Servier/Allogene)
  • UCART123 (Cellectis)
  • CTL119 (huCART19; Novartis)

KOLs interviewed

KOLs from North America

  • Joseph Mikhael, Professor at the Translational Genomics Research Institute (TGen) and Chief Medical Officer of the International Myeloma Foundation, Phoenix, AZ.
  • Susan R. Rheingold, Medical Director of the Oncology Outpatient Clinic and an Attending Physician with the Cancer Center, Children's Hospital of Philadelphia, PA.
  • Craig S. Sauter, Hematologic Oncologist and Clinical Director at the Memorial Sloan Kettering Cancer Center, New York, NY.
  • Michael R. Verneris, Professor and Director of Bone Marrow Transplantation and Cellular Therapy at Children's Hospital Colorado, Denver, CO.
  • Anonymous US KOL, Director of cell therapy and transplantation at a major centre for CAR-T cell research.

KOLs from Europe

  • Persis Amrolia, Professor of Transplantation Immunology, UCL Great Ormond Street Institute of Child Health, London, UK.
  • Monique Minnema, Professor of Haematology, University Medical Center Utrecht, Netherlands.
  • Anonymous KOL, Professor and specialist in CAR-T therapy at a major university hospital in Germany.

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