How are CAR-T and monoclonals reshaping the ALL treatment landscape?
Recent high-profile approvals for the CAR-T therapy Kymriah, and monoclonal antibodies Blincyto and Besponsa have reignited interest in ALL. Do these therapies live up to the hype in terms of their current impact and future potential? With further CAR-T therapies in the pipeline, how will the future of this class evolve and could the allogeneic CAR-T product UCART19 provide an ‘off the shelf’ solution? TKIs have improved the prognosis for Ph-positive ALL, but how do oncologists choose between these drugs, and how could their use develop? Could ruxolitinib or currently approved TKIs make their mark in Ph-like ALL? Furthermore, the experts discuss whether the success of venetoclax in CLL and AML could be replicated in ALL.
In this report, you’ll learn about these issues and more, as 12 of the world’s leading KOLs offer candid insights on seven marketed therapies and seven pipeline drugs.
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- Amid much hype, Blincyto, Besponsa and Kymriah have broken into the ALL space. How has their availability changed the treatment of this malignancy and how is their use expected to evolve?
- The ‘next-generation’ allogeneic CAR-T product UCART19 could constitute an effective therapy without the logistical baggage associated with autologous therapies. But how do KOLs rate its chances of success?
- With the advent of genetic profiling, increasing use of MRD testing and the introduction of new therapies, how will physicians negotiate this increasingly complex landscape?
- The FDA has granted accelerated approval for Blincyto in the treatment of adults and children who are in remission, but have detectable MRD. How do KOLs view the use of Blincyto in the MRD setting?
- The labelling for Besponsa carries a warning of the drug’s potential to induce hepatotoxicity, including hepatic veno-occlusive disease and increased risk of post-hematopoietic stem cell transplant non-relapse mortality. How concerned are KOLs by Besponsa’s toxicity profile and how does this shape its use?
- Venetoclax has demonstrated impressive efficacy in CLL and AML. Could this success be replicated in ALL?
- TKIs have improved outcomes for Ph-positive patients. How will their use evolve and could they have a role in the treatment of Ph-like ALL?
- The IntReALL Inter-European study group is conducting a large Phase III trial combining epratuzumab with chemotherapy in children with relapsed ALL. Could this trial establish a role for epratuzumab in the treatment of paediatric ALL?
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“I think blinatumomab and inotuzumab will show efficacy in the upfront setting. The next step will be to see if they can replace phases of chemotherapy. I think CAR-T cell therapy is going to move to the upfront setting for certain patients. Overall, immunotherapies will be more prominent in the relapsed setting and start to move upfront.”
US Key Opinion Leader
“We’re going to see improved survival in adults like we’ve seen in children over the past several decades. Most adults are going to be cured of ALL. We’ll use a combination of these drugs. We’ll start them individually, but we’re going to be using a lot of cocktails and sequencing.”
US Key Opinion Leader
“ALL therapy is witnessing a renaissance. This is a time for great excitement, starting with blinatumomab, which is activating the host T-cells, and with CAR-T.”
EU Key Opinion Leader
Sample of therapies covered
- Kymriah (tisagenlecleucel; Novartis)
- Blincyto (blinatumomab; Amgen)
- Besponsa (inotuzumab ozogamicin; Pfizer)
- MabThera/Rituxan (rituximab; Roche)
- Sprycel (dasatinib; Bristol-Myers Squibb)
- Iclusig (ponatinib; Takeda/Incyte)
- Gleevec/Glivec (imatinib; Novartis)
- Epratuzumab (Immunomedics)
- Ruxolitinib (Jakafi; Incyte)
- UCART19 (Cellectis/Servier/Pfizer/Allogene)
- Axicabtagene ciloleucel (Yescarta; Gilead)
- Daratumumab (Darzalex; Janssen)
- Ofatumumab (Arzerra; Novartis)
- Venetoclax (Venclexta/Venclyxto; AbbVie/Roche)
KOLs from North America
- Michael J Burke, MD, Associate Professor, Division of Hematology/Oncology/Blood & Marrow Transplantation, Children’s Hospital of Wisconsin, Milwaukee, WI
- Ryan Cassaday, MD, Assistant Professor, Division of Hematology, University of Washington School of Medicine, Seattle, WA
- Thomas R Chauncey, MD, PhD, Associate Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA
- Jorge E Cortes, MD, Deputy Chair and Professor of Medicine, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX
- Elias J Jabbour, MD, Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
- Michael R Verneris, MD, Professor and Director of Bone Marrow Transplantation and Cellular Therapy at Children's Hospital Colorado, Denver, CO
KOLs from Europe
- Roberto Foa, MD, Professor and Head of the Division of Haematology, Sapienza University and Policlinico Umberto I, Rome, Italy
- Oliver G Ottmann, MD, PhD, Professor and Head of Haematology, Division of Cancer and Genetics, Cardiff University, Cardiff, UK
- Rob Pieters, MD, PhD, Professor of Paediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, NetherlandsB4
- José María Ribera, MD, PhD, Associate Professor of Medicine, Autonomous University of Barcelona, Barcelona, Spain
- Xavier Thomas, MD, PhD, Hospices Civils de Lyon, Lyon-Sud Hospital, Department of Clinical Hematology, Pierre Bénite, Lyon, France
- Anonymous German KOL, Head of Oncology at a major university hospital, Germany
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