Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL.
The high complete remission rate with first-line combined fludarabine, cyclophosphamide, and rituximab (FCR) begs the question of the value of minimal residual disease (MRD)-negative status as a treatment end point. We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR. MRD was prospectively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment. After course 3 and at final response assessment, 17% and 43% of patients were MRD negative in bone marrow, respectively. A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses (MVAs). MRD-negative status was independently associated with significantly longer progression-free survival (PFS) and overall survival (OS) in MVA (P = .03 and .02, respectively). This association was confirmed also on landmark MVA at the time of MRD assessment (P = .04 and .05, respectively). MRD-negative patients had comparable PFS and OS, independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment. This trial was registered at www.clinicaltrials.gov as #NCT00759798.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Paolo
P
Strati
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Michael J
MJ
Keating
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Susan M
SM
O'Brien
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Jan
J
Burger
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Alessandra
A
Ferrajoli
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Nitin
N
Jain
Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Napoli, Italy; and.
Francesco Paolo
FP
Tambaro
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Zeev
Z
Estrov
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Jeffrey
J
Jorgensen
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Pramoda
P
Challagundla
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Stefan H
SH
Faderl
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
William G
WG
Wierda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D012074:Remission Induction; D000069283:Rituximab; D013997:Time Factors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D028761:Withholding Treatment / Q000706:statistics & numerical data
D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine