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CLL Updates From the 2019 ASH Annual Meeting |
Practice Community
New York, NY
Practice Niche
Chronic Lymphocytic Leukemia (CLL); Lymphoproliferative Disorders
Hospital and Institutional Affiliations
Director, CLL Program, Memorial Sloan Kettering Cancer Center
Question What data in chronic lymphocytic leukemia (CLL) that came out of the American Society of Hematology (ASH) 2019 meeting were considered practice changing? |
Answer The most practice changing presentation at the meeting was by Jeff Sharman, MD, who presented the results of the ELEVATE TN trial.1 This trial was in treatment-naive patients with CLL and looked at the role of acalabrutinib alone or combined with obinutuzumab compared with obinutuzumab plus chlorambucil. |
Question What novel treatments for CLL that were highlighted during the meeting seem most promising? |
Answer There were several presentations of promising new treatments for CLL. The presentation I gave was on LOXO-305.2 [They were] very early data, but LOXO-305 is a new, noncovalent-binding BTK inhibitor studied in patients who had relapsed or refractory CLL. |
Question It was shown in a retrospective analysis that ibrutinib was the top-prescribed drug among said study population, but 24-month overall survival was highest for those who received bendamustine-rituximab.4 What do you make of these findings, and how should it guide future treatment decisions, if at all? |
Answer I think whenever you look at claims data it is very hard to draw any conclusions particularly because of the fact you don’t have a lot of patient information such as prognostic profiles or medical comorbidities, etc. That makes it hard to judge or make comparisons between groups of patients. The major concern here would be treatment selection bias based on study design. It would be like conducting a clinical trial but not knowing about the patients enrolled in either arm. These types of studies are informative in terms of practice patterns, selection of therapy, or what drug is used more commonly, but to draw survival comparisons from medical claims data is incredibly difficult to do. It can only be seen as hypothesis-generating. |
Question Combination ibrutinib plus venetoclax: Is undetectable minimal residual disease (MRD) a good surrogate endpoint for survival? Why or why not? |
Answer Undetectable MRD is a helpful endpoint and we will see this more in future studies. Probably the best use of MRD, at this time, is for designing therapies and trials that are focused on discontinuation of therapy. There are a lot of trials that have looked MRD as a prognostic marker, which is interesting, but the goal is to really have it drive treatment decision making. |
Question Given the fact that many patients with CLL discontinue treatment or undergo dose reductions5 is time-limited treatment in CLL6 ultimately the best approach to drug therapy in your opinion? Why or why not? |
Answer It is going to vary patient by patient. Certainly double or triple novel-novel combination therapy or time-limited therapy is a wonderful option for many patients, but it does often expose patients for a fixed duration to multiple drugs at once, which potentially exposes them to more adverse events. Those therapies are most appropriate for patients with poor-risk features who would not do as well with single targeted agents or targeted agents paired with anti-CD20 monoclonal antibodies. It is not going to be the answer for everybody, unless one can prove that the intent of a particular combination is [of] curative intent as opposed to an aim of disease control. |
Question Chimeric antigen receptor T-cell (CAR-T) therapies in CLL: What were some of the most interesting insights from the data presented on adoptive cell therapies in CLL? |
Answer There were limited data about CAR-T in CLL presented at ASH this year. The one that comes to mind was given by Tanya Siddiqi during the oral sessions.7 In a population of heavily pretreated patients with CLL who had progressed on ibrutinib, more than 80% responded to CD-19 directed CAR-T therapy. There were also some durable remissions in a minority of patients with CLL. Immunotherapy, in the form of cellular therapy — whether it’s transplant or CAR-T — is still very much experimental. They are not currently approved for CLL and are not yet the standard of care. Right now, we are existing in a space with so many effective targeted agents for CLL. CAR-T will play a role, but it is hard to know where in the sequence of therapies it will fit. |
Disclosures: Dr Mato has done consulting, served on advisory boards, and/or received research funding from AbbVie, Acerta, AstraZeneca, Celgene, DTRM Biopharma, Genentech, Gilead, Janssen, Johnson & Johnson, Sunesis, and TG Therapeutics.
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