Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib.
OBJECTIVE
There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable therapy adherence.


METHODS
Eighty-seven patients with chronic-phase CML treated with imatinib 400 mg/d for a median of 59.7 months (range, 25 to 104 months) who had achieved complete cytogenetic response had adherence monitored during a 3-month period by using a microelectronic monitoring device. Adherence was correlated with levels of molecular response. Other factors that could influence outcome were also analyzed.


RESULTS
Median adherence rate was 98% (range, 24% to 104%). Twenty-three patients (26.4%) had adherence <or= 90%; in 12 of these patients (14%), adherence was <or= 80%. There was a strong correlation between adherence rate (<or= 90% or > 90%) and the 6-year probability of a 3-log reduction (also known as major molecular response [MMR]) in BCR-ABL1 transcripts (28.4% v 94.5%; P < .001) and also complete molecular response (CMR; 0% v 43.8%; P = .002). Multivariate analysis identified adherence (relative risk [RR], 11.7; P = .001) and expression of the molecular human organic cation transporter-1 (RR, 1.79; P = .038) as the only independent predictors for MMR. Adherence was the only independent predictor for CMR. No molecular responses were observed when adherence was <or= 80% (P < .001). Patients whose imatinib doses were increased had poor adherence (86.4%). In this latter population, adherence was the only independent predictor for inability to achieve an MMR (RR, 17.66; P = .006).


CONCLUSIONS
In patients with CML treated with imatinib for some years, poor adherence may be the predominant reason for inability to obtain adequate molecular responses.
Marin
David
D
Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Rd, London W12 0NN, United Kingdom. d.marin@imperial.ac.uk
Bazeos
Alexandra
A
Mahon
Francois-Xavier
FX
Eliasson
Lina
L
Milojkovic
Dragana
D
Bua
Marco
M
Apperley
Jane F
JF
Szydlo
Richard
R
Desai
Ritti
R
Kozlowski
Kasia
K
Paliompeis
Christos
C
Latham
Victoria
V
Foroni
Letizia
L
Molimard
Mathieu
M
Reid
Alistair
A
Rezvani
Katy
K
de Lavallade
Hugues
H
Guallar
Cristina
C
Goldman
John
J
Khorashad
Jamshid S
JS
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D020732:Cytogenetic Analysis; D016903:Drug Monitoring / Q000295:instrumentation; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation; D008875:Middle Aged; D009154:Mutation; D050811:Octamer Transcription Factor-1 / Q000235:genetics; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001549:Benzamides; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; C406060:abl-bcr fusion protein, human; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
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