Abstract

Background

Availability of the tyrosine kinase inhibitors (TKIs) has revolutionized the outcome of patients with CML, with a 10-year overall survival rate of approximately 90%. This long-term benefit is highly dependent upon adherence; patients with less than 90% TKI adherence have been shown to have poor outcomes. The primary aim of this retrospective observational study is to determine the association between adherence to first-line TKIs and response in community-based CML patients. The secondary aim is to describe the real-world effectiveness of first-line TKIs by evaluating rates of response and disease progression.

Methods

The McKesson Specialty Health/US Oncology Network (USON) iKnowMed (iKM) electronic health record (EHR) database and medical charts were used to identify newly diagnosed CML patients who received first-line TKIs between July 2007 and March 2011. Adherence to TKI was measured as proportion of days covered (PDC). PDC was computed as the actual number of days of TKI therapy divided by the number of follow-up days after TKI initiation. Adherence was defined as PDC ≥90%. Response assessment included complete hematologic response (CHR) at 3 and 6 months (mo), complete cytogenetic response [CCyR (FISH or karyotype)] at 12 and 18 mo, and major molecular response [MMR (BCR-ABLIS ≤0.1% or ≥3 log reduction)] at 12 and 18 mo. Disease progression was defined as transformation to accelerated phase (AP) or blast phase (BP) CML, bone marrow transplant (BMT), or all-cause of death during follow-up. Descriptive analysis was conducted to summarize baseline patient characteristics and progression. Fisher's exact test will be used to determine univariate association between adherence and response. Here we report the interim results for imatinib adherence and treatment response. Data collection for dasatinib/nilotinib is ongoing and will be presented.

Results

Three-hundred newly diagnosed CML patients were identified within the iKM database (195 imatinib, 54 dasatinib, and 51 nilotinib). Among 218 patients evaluated thus far, 155 (71.1%) received imatinib, 28 (12.8%) received dasatinib, and 35 (16.1%) received nilotinib. Baseline patient characteristics were well balanced across the TKIs. Mean PDC for imatinib was 80%; 58% (n=117) were adherent (PDC≥90%). Imatinib treatment response data is presented in Table 1 according to adherence status. Low frequency of response monitoring limited the number of patients for analysis (47% evaluable for cytogenetic response and 67% for molecular response within the first 18 mo of treatment). Within a median follow-up of 38 mo, 25 (16%) imatinib patients progressed during the follow-up period (9 transformed to AP/BP, 4 BMT, 12 deaths). Overall, there were 14 deaths among imatinib treated patients.

Table 1

Imatinib adherence and response data

 CHR 6 mo CCyR 12 mo CCyR 18 mo MMR 12 mo MMR 18 mo 
Overall patients tested (n) 102 64 73 98 104 
Patients who achieved response, n (%) 89 (87) 33 (51) 42 (57) 22 (22) 34 (32) 
Patients tested and evaluated for adherence (n) 83 48 55 75 79 
Total number of patients who achieved response 73 23 30 20 29 
- Adherent patients who achieved response, n (%) 51 (91) 14 (56) 19 (65) 14 (31) 21 (45) 
- Non-adherent patients who achieved response, n (%) 22 (81) 9 (39) 11 (42) 6 (19) 8 (24) 
 CHR 6 mo CCyR 12 mo CCyR 18 mo MMR 12 mo MMR 18 mo 
Overall patients tested (n) 102 64 73 98 104 
Patients who achieved response, n (%) 89 (87) 33 (51) 42 (57) 22 (22) 34 (32) 
Patients tested and evaluated for adherence (n) 83 48 55 75 79 
Total number of patients who achieved response 73 23 30 20 29 
- Adherent patients who achieved response, n (%) 51 (91) 14 (56) 19 (65) 14 (31) 21 (45) 
- Non-adherent patients who achieved response, n (%) 22 (81) 9 (39) 11 (42) 6 (19) 8 (24) 
Conclusion

Among newly diagnosed CML patients who received imatinib in a community practice setting, the rates of 12-mo CCyR and MMR were 51% and 22%, respectively. In addition, 16% of imatinib-treated patients progressed during a median follow-up period of 38 mo. Fifty-eight percent of imatinib patients were adherent; these patients were observed to have higher cytogenetic and molecular responses compared to non-adherent patients. Response assessment within this study was limited by the low frequency of cytogenetic and molecular monitoring within clinical practice; USON is initiating measures to improve compliance to response monitoring guidelines.

Disclosures:

Bhowmik:McKesson Specialty Health/US Oncology Network: Employment. Bhor:McKesson Specialty Health/US Oncology Network: Employment. Yap:McKesson Specialty Health/US Oncology Network: Employment. Middlebrook:McKesson Specialty Health/US Oncology Network: Employment. Rembert:McKesson Specialty Health/US Oncology Network: Employment. Cain:Bristol-Myers Squibb: Employment. Okoro:Bristol-Myers Squibb: Employment. Bolinder:Bristol-Myers Squibb: Employment. Jabbour:Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Ariad: Honoraria.

Author notes

*

Asterisk with author names denotes non-ASH members.