Combinations or sequences of targeted agents in CLL: Is the whole greater than the sum of its parts (Aristotle, 360 BC)? Journal Article


Authors: Yazdy, M. S.; Mato, A. R.; Cheson, B. D.
Article Title: Combinations or sequences of targeted agents in CLL: Is the whole greater than the sum of its parts (Aristotle, 360 BC)?
Abstract: The treatment landscape for chronic lymphocytic leukemia (CLL) is rapidly evolving. Targeted agents (TAs) have demonstrated impressive single agent activity and therefore have been replacing chemoimmunotherapy (CIT). Despite their efficacy, the optimal use of the current TAs remains challenging. Perhaps the major dilemma is whether these drugs are best used in sequence or in combinations. Most patients tolerate TA well, notably early during treatment; however, a substantial number discontinue therapy because of toxicities. Therefore, the reasons for discontinuation and, subsequently, the preferred sequence of these agents become critical issues. Although TA monotherapy has revolutionized the treatment of CLL, residual disease, acquired resistance, suboptimal durability of response in patients with high-risk disease, indefinite treatment duration, and decreased compliance over time are issues of concern. To address these challenges, an increasing number of studies are evaluating different combinations of TAs; however, these studies have been mostly small single arm trials in heterogeneous patient populations using different methods for response assessment. A number of questions remain regarding the predictive value of minimal residual disease (MRD) status, durability of response, fixed treatment durations, and importantly, criteria for selection of patients for the optimal combinations. Medical comorbidities, performance status, prior therapies, and disease risk profile are fundamental in determining the treatment plan for each individual patient. Furthermore, utilizing prognostic and predictive markers along with monitoring MRD can guide the development of individualized, better-tolerated, time-limited, and potentially curative chemo-free treatment regimens. © 2019 by The American Society of Hematology.
Journal Title: Blood
Volume: 133
Issue: 2
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2019-01-10
Start Page: 121
End Page: 129
Language: English
DOI: 10.1182/blood-2018-08-869503
PUBMED: 30429158
PROVIDER: scopus
DOI/URL:
Notes: Review -- Export Date: 1 February 2019 -- Source: Scopus
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MSK Authors
  1. Anthony R Mato
    16 Mato