The introduction of the first targeted tyrosine kinase inhibitor (TKI), imatinib mesylate (IM) revolutionized the therapeutic paradigm and dramatically improved outcomes of chronic myeloid leukemia(CML). Data are limited in developing countries regarding the clinicopathologic features and response to therapy in the era of IM.
To report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400mg daily as frontline therapy and to determine imatinib’s efficacy and safety.
From October 2002 to December 2011, two hundred and ninety two CML patients were treated with IM in 6 Tunisian departments of hematology. Monitoring response was defined as the ELN provided guidelines. Response (Hematologic, cytogenetic and molecular responses), adverse events and outcome (overall survival, event free survival and progression free survival) were evaluated. The factors associated with outcome of IM therapy were also analyzed.
Two hundred ninety-two patients enrolled with a median follow-up duration of 56 (8 -290) months: The median age was 44 years (3-78 years). One hundred and fifty (51.3%) patients were male, 134 (49%) were asymptomatic at diagnosis. Splenomegaly was present in 237 of 292 (81%). Additional cytogenetic abnormalities were encountred in 24 (8.3%) patients. At diagnosis, 271 (92.8%) patients were in CP, 21 (7.2%) were in AP. The Sokal risk was low in 64 (23%), intermediate in 94 (33.5%), and high in 122 patients (43.5%). The Eutos risk was low in 179 (75%), and high in 60 (25%) patients.The rate of cumulative complete hematologic response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR) and molecular response 4/5 log (CMR) in CP/AP CML patients were 93.8%, 73%, 65% and 33.9%, respectively. According to the 2009 ELN criteria, optimal, suboptimal response and failure were noted in 132 (47%), 68 (24%) and 82 (29%) patients, respectively. Five year event free survival (EFS), progression free survival (PFS) and overall survival (OS) were 78%, 89% and 91%, respectively. By multivariate analyzis, AP, high Eutos risk and baseline WBC ≥ 150G/l remained independent predictive factors of non optimal response to IM. AP was an adverse independent prognostic factor for EFS, PFS and OS. Patients obtained CCyR at 12 months after the initiation of IM treatment were associated with longer PFS (P< 0.0001) and OS (P< 0.0001). ELN response was also significantly associated with EFS. The adverse events (AE) of IM were moderate and tolerable. Only 3 patients discontinued IM for intolerance. IM-related hematologic AE included neutropenia in 6.2%, anemia in 8.9%, and thrombocytopenia in 17.2%. Nonhematologic AE (21%), including mainly edema in 7.1%, digestive disorders in 5.5%, weight gain and skin rash in 3.1%.
We found that substantial number of patients in our series were in intermediate or high risk group. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The front-line use of 2nd TKI are expected to improve the results of the first line treatment of these high risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.