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Ferrata Storti Foundation
Haematologica 2019 Volume 104(8):1532-1541
How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia?
Nicholas J. Short and Farhad Ravandi
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
ABSTRACT
Assessment of measurable residual disease, also called “minimal resid- ual disease,” in patients with acute myeloid leukemia in morpholog- ical remission provides powerful prognostic information and comple- ments pretreatment factors such as cytogenetics and genomic alterations. Based on data that low levels of persistent or recurrent residual leukemia are consistently associated with an increased risk of relapse and worse long- term outcomes, its routine assessment has been recommended by some experts and consensus guidelines. In addition to providing important prog- nostic information, the detection of measurable residual disease may also theoretically help to determine the optimal post-remission strategy for an individual patient. However, the full therapeutic implications of measurable residual disease are uncertain and thus controversy exists as to whether it should be routinely incorporated into clinical practice. While some evidence supports the use of allogeneic stem cell transplantation or hypomethylating agents for some subgroups of patients in morphological remission but with detectable residual leukemia, the appropriate use of this information in mak- ing clinical decisions remains largely speculative at present. To resolve this pressing clinical issue, several ongoing studies are evaluating measurable residual disease-directed treatments in acute myeloid leukemia and may lead to new, effective strategies for patients in these circumstances. This review examines the common technologies used in clinical practice and in the research setting to detect residual leukemia, the major clinical studies establishing the prognostic impact of measurable residual disease in acute myeloid leukemia, and the potential ways, both now and in the future, that such testing may rationally guide therapeutic decision-making.
Introduction
Acute myeloid leukemia (AML) is a heterogeneous disease, with a widely vari- able likelihood of cure with conventional therapies that depends on both patient- and disease-related characteristics.1 Historically, pretreatment characteristics such as the patients’ age, karyotype, and, more recently, genetic mutations have been the primary determinants of prognosis in patients with newly diagnosed AML. How well the leukemia responds to initial treatment also provides important infor- mation about chemosensitivity of an individual’s leukemia that cannot always be predicted from pretreatment characteristics. One measure of treatment response is the achievement of complete remission, defined as bone marrow with <5% blasts with recovery of peripheral blood elements and no evidence of extramedullary dis- ease.2 However, among patients <60 years of age who achieve complete remission with induction and then receive consolidation chemotherapy, the cure rate is only approximately 50% (and significantly lower in older patients), suggesting that mor- phological assessment of the bone marrow alone is inadequate to discriminate relapse risk.3 Accurate assessment of the risk of relapse is imperative in the treat- ment of AML, as the decision to pursue consolidation chemotherapy rather than allogeneic hematopoietic stem cell transplantation (HSCT) in first remission is largely decided by the anticipated risk of relapse in the absence of HSCT balanced against the risk of relapse after HSCT as well as the expected transplant-related
Correspondence:
FARHAD RAVANDI
fravandi@mdanderson.org
Received: February 8, 2019. Accepted: June 5, 2019. Pre-published: July 4, 2019.
doi:10.3324/haematol.2018.208454
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/8/1532
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