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Cancer Therapy: Clinical

This analysis does not take into account the time difference in follow-up between patients. Thus, to adjust for the time to achieving molecular response, we repeated the multivariate analysis considering achieving a major or complete molecular remission at 12 months as the end point. For this analysis, we focused on patients treated in early chronic phase as this is the setting where most patients are currently being treated with imatinib, and for these patients, the percentage of Ph-positive metaphases <90% rarely applies. In this analysis, treatment with high-dose imatinib was the only variable associated with an increased probability of achieving a major (P = 0.01) or complete molecular response (P = 0.02).

Durability of cytogenetic response by molecular response. We then investigated the long-term clinical significance of achieving a molecular response (Table 3). Because of the small number of deaths and transformations during therapy, the analysis of the clinical implications of molecular response

focused on duration of complete cytogenetic remission. Patients achieving a major molecular response were followed for a median of 31 months (range, 7.5-52 months) from the start of imatinib therapy. Eight patients achieved a major molecular response only on their last evaluation and therefore have no follow-up at the time of this report. Among the 166 patients who had at least one additional cytogenetic analysis after achieving a major molecular response, 9 (5%) lost their complete cytogenetic remission, compared with 25 of 68 (37%) who did not achieve a major molecular response (P = 0.0001). Two and four patients eventually re-gained a complete cytogenetic remission, respectively (one after in- creasing the dose of imatinib, all others without additional intervention). Patients with undetectable levels of BCR-ABL were followed for a median of 14 months (range, 3-27 months) after reaching this milestone, not considering 13 who became undetectable only on their latest follow-up

<60

199

122 (61)

z60

81

52 (64)

No

232

148 (64)

Yes

48

26 (54)

<12

110

63 (57)

z12

169

110 (65)

V20

159

97 (61)

20.1-50

64

44 (69)

>50

56

32 (57)

V450

205

120 (58)

>450

75

54 (72)

<7

238

151 (63)

z7

42

23 (55)

0-1

254

163 (64)

2

18

9 (50)

z3

8

2 (25)

<4

220

140 (64)

z4

60

34 (57)

<5

261

166 (64)

z5

19

8 (42)

No

258

159 (62)

Yes

21

14 (67)

Low

98

76 (78)

Intermediate

69

41 (59)

High

34

18 (53)

V90

56

39 (70)

>90

221

134 (61)

<12

175

112 (64)

12-35

65

36 (55)

z36

40

26 (65)

ECP

163

110 (67)

IFN failure

117

64 (55)

400

144

77 (53)

800

136

97 (71)

Abbreviations: MMR, major molecular response; CMR, complete molecular response; ECP, early chronic phase. *Two hundred and one patients evaluable.

CMR

65 (33) 30 (37) 77 (33) 18 (38) 36 (33) 59 (35) 61 (38) 17 (26) 17 (30) 63 (31) 32 (43) 79 (33) 16 (38) 89 (35) 5 (28) 1 (12) 79 (36) 16 (27) 91 (35) 4 (21) 84 (32) 10 (48) 34 (35) 26 (38) 9 (26) 27 (48) 67 (30) 54 (31) 27 (42) 14 (35) 52 (32) 43 (37) 42 (29) 53 (39)

0.20

0.35

0.53

0.02

0.30

0.47

0.11

% Ph at pretreatment

Duration of chronic phase (months)

Study group

Starting dose of imatinib (mg)

P 0.57

0.08

0.60

0.22

Marrow basophils (%)

Marrow blasts (%)

Cytogenetic clonal evolution

Sokal risk*

0.28

0.49

0.04

0.003

0.62

0.80

0.32

0.23

Table 2. Associations of patient and disease characteristics with molecular response (n = 280)

Platelets (109/L)

Peripheral basophils (%)

Peripheral blasts (%)

0.008

0.04

0.40

Variables Age (y)

Splenomegaly

Hemoglobin (g/dL)

WBC (109/L)

Category

n

MMR

0.06

0.30

0.08

0.82

0.39

P 0.75

0.25

0.23

Clin Cancer Res 2005;11(9) May 1, 2005

3428

www.aacrjournals.org

Downloaded from clincancerres.aacrjournals.org on February 5, 2015. © 2005 American Association for Cancer Research.

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