Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL

作     者：Thompson, Philip A. Wierda, William G. 

作者机构：Univ Texas MD Anderson Canc Ctr Dept Leukemia Houston TX 77030 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：2016年第127卷第3期

页      面：279-286页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：National Institutes of Health, NIH, (P30CA016672) National Cancer Institute, NCI, (P01CA081534) Haematology Society of Australia and New Zealand 

主　　题：Antineoplastic Combined Chemotherapy Protocols/therapeutic use Clinical Decision-Making Flow Cytometry/methods Flow Cytometry/methods Hematopoietic Stem Cell Transplantation Humans Immunotherapy/methods Leukemia, Lymphocytic, Chronic, B-Cell/mortality Leukemia, Lymphocytic, Chronic, B-Cell/pathology Leukemia, Lymphocytic, Chronic, B-Cell/therapy Neoplasm Staging Neoplasm Staging Neoplasm, Residual/diagnosis Neoplasm, Residual/therapy Polymerase Chain Reaction/methods Treatment Outcome 

摘      要：Deep remission and prolonged disease-free survival can be achieved with first-line chemoimmunotherapy (CIT), such as combined fludarabine, cyclophosphamide, and rituximab, in the majority of patients with chronic lymphocytic leukemia (CLL). More modest results are reported with less intense regimens like obinutuzumab plus chlorambucil. Clinical assessment has limited sensitivity indetecting residualdisease responsible for subsequent relapse, even including morphologic bone marrow (BM) evaluation. Multicolor flow cytometry and polymerase chain reaction (PCR)-based methods can detect minimal residual disease (MRD) to a sensitivity of = 1: 10 000 (10(-4)). Achieving BM MRD-negative complete remission (CR) is associated with superior progression-free survival (PFS) and overall survival;MRD status is the single best posttreatment predictor of long-term outcomes after CIT. Newer oral B-cell receptor signaling pathway inhibitors are highly effective at controlling disease, but best monotherapy responses are typically partial remission, and patients must remain on treatment to maintain disease control. Therapeutic progress is still needed for CLL. We propose that targeting MRD provides opportunity to realize this progress. Achieving BM MRD-negative CR is a prerequisite for long-term unmaintained disease-free survival and potential for cure. We review available methodologies for detecting MRD and correlations with posttreatment outcomes. We discuss the potential utility of MRD to direct individualized therapy. Finally, we discuss the importance of MRD negative status as a surrogate marker for longer PFS in clinical studies to allow more rapid determination of clinical benefit.