Abstract

Abstract 3750

Background:

The WORLD CML Registry is a multinational, prospective registry established to longitudinally assess global patterns of current and evolving methods for diagnosis, treatment, and clinical outcome measures in pts with CML and to compare clinical practice patterns to management recommendations provided by the European LeukemiaNet (ELN; Baccarani M, et al. J Clin Oncol. 2009;27:6041–6051). Here, we report overall efficacy and safety data from this registry, as well as clinical monitoring practices and outcomes in the subgroup of pts with CML in chronic phase (CP) treated with first-line imatinib.

Methods:

Pts (≥ 16 y of age) with CML in CP, accelerated phase (AP), or blast crisis (BC) within 6 mo + 2 weeks of confirmed CML diagnosis were enrolled at sites in Latin America, Asia-Pacific, the United States, Russia, Turkey, the Middle East, and Africa. Baseline demographics and medical history were collected at enrollment; disease status and management information were collected at approximate 6-mo intervals or when there was a change in disease status/management. Adverse events (AEs) were collected only if they resulted in a dose/regimen change, nonadherence to treatment, or death.

Results:

A total of 1837 of the 1889 pts enrolled between February 2008 and December 31, 2010, were evaluable (ie, had confirmed informed consent forms and no protocol deviations) and are the basis for this analysis. Median age was 47 y (range, 16–92 y), and 58% of pts were male. CML diagnosis was established using hematologic (91% of pts), bone marrow (82%), cytogenetic (83%), and molecular (polymerase chain reaction [PCR]; 53%) assessments. Nearly all pts (94%) were initially diagnosed in CP (Table). As of the data cutoff (December 31, 2010), median overall survival (OS) and median event-free survival (EFS) in all pts were not reached. Estimated OS and EFS rates at 3 y were 90.4% and 74.8%, respectively. AEs reported in ≥ 1% of pts were thrombocytopenia (3%) and neutropenia (2%). In the CML-CP subgroup, imatinib (Glivec®/Gleevec®) was administered as first-line therapy (in clinical practice or in a clinical trial) to 63% of pts (n = 1083). Disease burden in CML-CP pts on imatinib over time was most commonly assessed via blood counts (Table). Cytogenetic and molecular assessments were used in a minority of CML-CP pts at most time points. Only 50% of pts had a disease assessment at 3 mo (hematologic, 49%; cytogenetic, 10%; molecular, 15%). Of the pts on first-line imatinib outside of a clinical trial setting (n = 1024), 95 (9%) had their dose increased, 77 (8%) had their dose decreased, and 82 (8%) were switched to nilotinib or dasatinib. In all CML-CP pts treated with first-line imatinib, estimated OS and EFS rates at 3 y were 92.1% and 76.6%, respectively (Table). Estimated OS and EFS rates at 3 y were higher in pts who had higher imatinib exposure (treatment received ≥ 85% of total days) vs pts who received imatinib treatment on < 85% of days.

Conclusions:

The majority of CML-CP pts treated with first-line imatinib did not have cytogenetic or molecular assessments in accordance with current ELN recommendations, particularly at early time points. Additionally, pts who had higher drug exposure to imatinib had higher estimated OS and EFS rates at 3 y than those who did not.

Initially Diagnosed Phase of CML, n (%) Evaluable Pts (N = 1837)  
    CP 1727 (94)  
    AP 75 (4)  
    BC 35 (2)  
OS/EFS Estimated OS/EFS rates at 3 y,* % (95% CI) Median OS/EFS, mo 
    All pts 90.4 (87.8–92.5)/74.8 (69.9–79.1) NR/NR 
    CML-CP pts 91.8 (89.1–93.9)/77.3 (72.2–81.6) NR/NR 
    CML-CP pts treated with first-line imatinib 92.1 (88.3–94.7)/76.6 (68.9–82.7) NR/NR 
        Imatinib exposure on ≥ 85% of days (n = 746) 95.0 (89.9–97.6)/84.5 (71.9–91.8) NR/NR 
        Imatinib exposure on < 85% of days (n = 337) 85.4 (78.2–90.4)/56.8 (48.4–64.3) NR/NR 
Initially Diagnosed Phase of CML, n (%) Evaluable Pts (N = 1837)  
    CP 1727 (94)  
    AP 75 (4)  
    BC 35 (2)  
OS/EFS Estimated OS/EFS rates at 3 y,* % (95% CI) Median OS/EFS, mo 
    All pts 90.4 (87.8–92.5)/74.8 (69.9–79.1) NR/NR 
    CML-CP pts 91.8 (89.1–93.9)/77.3 (72.2–81.6) NR/NR 
    CML-CP pts treated with first-line imatinib 92.1 (88.3–94.7)/76.6 (68.9–82.7) NR/NR 
        Imatinib exposure on ≥ 85% of days (n = 746) 95.0 (89.9–97.6)/84.5 (71.9–91.8) NR/NR 
        Imatinib exposure on < 85% of days (n = 337) 85.4 (78.2–90.4)/56.8 (48.4–64.3) NR/NR 
Disease Assessments in CML-CP Pts Treated with First-Line Imatinib 
 Time Since Start of Imatinib 
 3 mo (n = 1083) 6 mo (n = 1034) 12 mo (n = 931) 18 mo (n = 707) 2 y (n = 453) 3 y (n = 111) 
Pts with assessment, n (%) 546 (50) 777 (75) 788 (85) 558 (79) 374 (83) 78 (70) 
    Hematologic, n (%) 528 (49) 747 (72) 756 (81) 522 (74) 353 (78) 75 (68) 
    Cytogenetic, n (%) 109 (10) 399 (39) 354 (38) 188 (27) 119 (26) 22 (20) 
    Molecular, n (%) 167 (15) 401 (39) 468 (50) 320 (45) 225 (50) 49 (44) 
Disease Assessments in CML-CP Pts Treated with First-Line Imatinib 
 Time Since Start of Imatinib 
 3 mo (n = 1083) 6 mo (n = 1034) 12 mo (n = 931) 18 mo (n = 707) 2 y (n = 453) 3 y (n = 111) 
Pts with assessment, n (%) 546 (50) 777 (75) 788 (85) 558 (79) 374 (83) 78 (70) 
    Hematologic, n (%) 528 (49) 747 (72) 756 (81) 522 (74) 353 (78) 75 (68) 
    Cytogenetic, n (%) 109 (10) 399 (39) 354 (38) 188 (27) 119 (26) 22 (20) 
    Molecular, n (%) 167 (15) 401 (39) 468 (50) 320 (45) 225 (50) 49 (44) 

NR, not reached.

*

OS event: death; EFS events: death or first occurrence of disease progression/recurrence.

n values show the number of pts still in the registry at each time point.

Includes fluorescence in situ hybridization.

Disclosures:

Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding. Kantarjian:Novartis Pharmaceuticals Corp: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Research Funding. Piccolo:Novartis Pharma AG: Employment. Zernovak:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Sivarathinasami:Novartis Healthcare Pvt. Ltd,: Employment. Eng:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Kim:Novartis: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ARIAD: Research Funding; II-Yang: Consultancy, Honoraria, Research Funding. Hughes:Novartis Pharmaceuticals Corp: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Ariad: Consultancy; CSL: Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.