Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens.
Although immunoglobulin V(H) mutation status (IgV(H) MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgV(H) somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgV(H) MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgV(H) than those whose CLL used mutated IgV(H) (TTP 47% vs 82% at 6 years, P < .001). In a multivariate model considering all baseline characteristics, IgV(H) MS emerged as the only determinant of remission duration (hazard ratio 3.8, P < .001). Our results suggest that postremission interventions should be targeted toward patients with unmutated IgV(H) status.
Lin
Katherine I
KI
Leukemia Department, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
Tam
Constantine S
CS
Keating
Michael J
MJ
Wierda
William G
WG
O'Brien
Susan
S
Lerner
Susan
S
Coombes
Kevin R
KR
Schlette
Ellen
E
Ferrajoli
Alessandra
A
Barron
Lynn L
LL
Kipps
Thomas J
TJ
Rassenti
Laura
L
Faderl
Stefan
S
Kantarjian
Hagop
H
Abruzzo
Lynne V
LV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011379:Prognosis; D011961:Receptors, Fc / Q000276:immunology; D000069283:Rituximab; D016019:Survival Analysis; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D011961:Receptors, Fc; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine