Affiliation:
1. Leukemia, MDACC, Houston
2. U of Calif, Los Angeles
3. U of Heildelberg, Mannheim
4. Karmanos Cancer Inst, Detroit
5. CHU La Miletri, Poitiers
6. U of Liepzig, Leipzig
7. Inst Nationale Tumori, Milan
8. Dana Farber, Boston
9. U of Mainz, Mainz
10. NHLBI, Bethesda
11. U of Mich, Ann Arbor
12. OHSU, Portland
Abstract
Abstract
Background: Imatinib is a selective inhibitor of the Bcr-Abl tyrosine kinase indicated for the treatment of all phases of Ph+ CML. This study updates the results up to more than 60 months (mos) after last patient (pt) started treatment.
Methods: Imatinib 400 mg/d was first administered to 454 patients with L-CP CML between December 1999 and May 2000. Median time since diagnosis was 34 months (mos). Pts had received a median of 14 mos of prior IFN treatment before entering the study but were hematologically (n=133) or cytogenetically resistant/refractory (n=160) or intolerant (n=161) to IFN. Dose escalation up to 800 mg/d was allowed for lack of efficacy. Pts were evaluated for best major and complete cytogenetic response (MCyR and CCyR), time to progression to accelerated phase (AP) or blast crisis (BC), and overall survival (OS). Beyond July 31, 2002, no adverse events or laboratory values were collected.
Results: As of July 31, 2005, median duration of treatment was 60 mos (with average of 48 mos). A total of 244 (54%) pts had their dose increased to 600 or 800 mg/d, 42% received 800 mg/d at least once. Of 227 pts who are still on treatment, 85 (37%) had their dose increased to 600 mg/d or 800 mg/d for lack of efficacy. Overall actual dose intensity was 444 mg/d (median 400mg/d). The table below summarizes reasons for discontinuation, best observed responses rates and estimated long term outcomes at 60 mos.
n (%) [95% conf. intervals] N=454 Still on treatment 227 (50) Discontinued 227 (50) Unsatisfactory therapeutic effect 117 (26) Deaths from any cause 18 (4) AEs & abnormal laboratory values 33 (7) BMT 5 (1) Withdrew consent/Lost/Others 54 (12) Pts with MCyR (incl CCyR) 304 (67) Pts with CCyR 259 (57) % Estimated freedom of progression to AP/BC at 60 mos 69% [64–74] % Estimated OS at 60 mos 79% [75–83]
The MCyR (CCyR) rate was 57% (48%) for hematologic failures to IFN, 70% (60%) in cytogenetic failures to IFN and 72% (62%) in IFN intolerant pts. A CCyR was achieved after more than 36 mos of treatment in 28 pts; 22 (79%) of these pts had achieved CCyR after dose increase to 600 or 800 mg.
Landmark analyses confirmed the effect of cytogenetic responses on long-term outcomes. The estimated survival rates free of AP/BC at 60 mos were 91%, 82%, 77%, 62% and 42% for pts who by 12 months achieved CCyR, PCyR, Minor CyR, Minimal CyR and no CyR, respectively (p<0.001). This corresponds to a rate of 88% in pts with MCyR at 12 mos. The estimated overall survival rates at 60 mos were 93%, 92%, 88%, 71% and 64% for pts who achieved CCyR, PCyR, Minor CyR, Minimal CyR and no CyR at this landmark, respectively (p<0.001). This corresponds to an overall survival rate of 93% in patients who had achieved MCyR at 12 mos.
Conclusion: Imatinib substantially improves the duration of CP-CML in pts who previously failed IFN. The follow-up confirms the beneficial effect of cytogenetic responses on long-term outcomes with imatinib. These results will be updated for the meeting to include 72 mos data up to July 31, 2006.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
2 articles.
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