iwNHL 2016: Highlights from Day 1

John Gribben, MD, DSc, FRCPath, FMed Sci of Barts Cancer Institute, London, UK discusses the highlights from the first day of the 2016 International Workshop on Non-Hodgkin Lymphoma (iwNHL) meeting held in San Diego, CA with Laurence de Leval, MD, PhD of University Hospital of Lausanne, Lausanne, Switzerland, Wyndham Wilson, MD, PhD of the National Cancer Institute, Bethesda, MD and Catherine Bollard, MBChB, MD, FRACP, FRCPA of the Children's National Health System, Washington, DC. First, Prof. de Leval discusses T-cell lymphoma and the advances in the understanding of its molecular pathogenesis. She points out that the WHO classification is being revised and that these novel discoveries have now been included. She further discusses the heterogeneity and grouping of these tumors. Prof. Gribben asks whether we can expect the advances that have been made in our understanding of the pathophysiology of T-cell lymphomas to lead to a paradigm shift in terms of treatment. Prof. de Leval first points out the difficulty of getting patients on trials, which is due to the rarity of these diseases and their heterogeneity. Further, one of the questions is how to identify patients who would be best candidates for stem cell transplantation. Prof. de Leval then discusses combinations and novel therapies, such as demethylating agents and HDAC inhibitors. Dr Wilson points that we can draw parallels to B-cell lymphomas as there is much heterogeneity in this group of disorders as well. An overarching abnormality has been B-cell receptor (BCR) signaling and also T-cell receptor (TCR) signaling. The next topic discussed is the challenges in the area of childhood lymphoma (e.g. if an 18 year old should be treated with pediatric or adult protocols). Dr Bollard discusses the treatment of the young adult (AYA) population. She points out that most pediatric oncologists come from an acute lymphoblastic leukemia (ALL) background, which affects their treatment approach. She highlights that there is a lot of controversy about how young patients should be treated and argues that pediatric and medical oncologists need to work on the design of trials for this population together. Prof. Gribben further asks if some cases are over-treated and Dr Bollard agrees that indeed some patients are being over-treated. However, the context is difficult as failure is not an option with young patients as the salvage rates are poor. Dr Wilson argues that this is a philosophical question as data from trials with adults are not being considered by pediatric oncologists. He points out that large cell lymphomas do not need high-dose methotrexate as shown from data from adults. Further, it has been shown that rituximab when applied in adults with CD20+ curable diseases, has improved outcome but it took a long time until this was investigated in pediatric patients. He also discusses radiotherapy and here Dr Bollard points out that radiation is being pulled back, even for Hodgkin lymphoma. She also emphasizes that the pediatric community cares about cardiotoxicity and has acted accordingly to adjust treatment. The next topic of discussion is salvage therapies and immunotherapy, with a focus on CAR T-cells. Dr Bollard points out that the studies discussed at the meeting on CD19 CAR T-cell therapy all use a different type of CAR and conditioning regiment. However, the results are all outstanding for a chemorefractory, heavily pre-treated diffuse large B-cell lymphoma (DLBCL) patient population. She highlights that this an exciting therapy but another question to consider is what about the other immunotherapies, such as checkpoint inhibitors, BiTEs and DARTs? Prof. Gribben asks if CAR T-cell therapy is ready for prime time or if it should remain a specialized field. Dr Wilson points out that many centers are doing CAR therapy and he worries that some institutions may not have the right expertise. Finally, they discuss circulating DNA as markers of disease. Dr Wilson explains that lot of time is spent imaging patients to determine if they are in complete remission (CR), which predicts long-term outcome. However, for indolent diseases for example, which are not considered curable, tests like this may allow us to understand that some of these patients are actually cured. Further, he believes that the notion that we don't cure patients with follicular lymphoma is probably not true. Finally, he discusses liquid biopsies is very exciting, which he considers an exciting area.
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