Sustained Responses and Resistance to Imatinib Mesylate in the First 173 Chronic Myeloid Leukemia Patients Accrued by the SCREEN Multicenter Study: First Interim Report.

Imatinib mesylate (IM) has shown unprecedented effectiveness in the treatment of Chronic Myeloid Leukemia (CML) patients (pts) in the chronic phase of the disease. As most of the data concerning the efficacy of the drug derive either from a single sponsored trial or from single institution reports, we decided to accrue all CML pts diagnosed in the Italian region of Sicily to the observational SCREEN (Siciliy CML Regional Enterprise) study, to evaluate the hematological, cytogenetic and molecular responses of this unselected population to IM.

Although the study is still ongoing, 173 consecutive CML pts have been enrolled between January 2005 and June 2009 (cutoff time for the first interim analysis) by one of the 12 institutions involved. Each center was responsible for the diagnosis, treatment (IM 400 mg qd) and follow-up of the pts accrued, while all molecular analyses were centralized in Catania. Median follow-up time was 31 months. Eleven pts (6.3%) are currently off study.

Pts characteristics were as follows: 95 males (54.9%) and 78 females (45.1%) were enrolled with a median age of 53 years (range 24-90). Eighty-nine pts (51.4%) were low Sokal risk, 62 (35.8%) were intermediate risk and 22 (12.8%) were high risk. Nine pts (5.2%) displayed additional chromosomal abnormalities. Median leukocyte counts (1×10⁹L) were 67.6 (range 3.4-718), median hemoglobin (g/L) was 122 (range 75-170) while median platelet counts (1×10⁹L) were 317 (range 67-2620). Cumulative incidences of complete hematologic response (CHR) and complete cytogenetic response (CCyR) were 98.3% and 85% respectively, while 59.2% of pts obtained a major molecular response (MMR). At 54 months, estimated overall survival was 95.6%. Estimated progression free survival (accounting for all pts that failed IM according to the European Leukemia Net criteria) was 75.1%. Thirty pts (17.3%) presented resistance to IM, either because of failure to obtain a satisfactory response (primary resistance, 21 pts) or because of loss of previously obtained responses (secondary resistance, 9 pts). Thirty-three pts (19%) presented a suboptimal response, 8 because of failure to achieve a CCyR by 12 months of therapy and the remaining 25 because of lack of a MMR after 18 months of IM. Only 3 pts (1.7%) were intolerant to IM. Interestingly, the median amount of BCR-ABL transcript at diagnosis (measured according to the International standardized Scale) displayed by pts that failed IM or achieved a suboptimal response (106.5^IS) was significantly higher than that of pts obtaining an optimal response (61.9 ^IS p=0.0031).

IM is a highly effective and well-tolerated treatment for most chronic phase CML pts, producing high rates of CHR and CCyR. Approximately 60% of cases will also achieve a MMR. 35-40% of pts will either fail IM or obtain only partially satisfying results (suboptimal response). High levels of BCR-ABL transcript at diagnosis might allow a rapid identification of this less responsive pt population.

No relevant conflicts of interest to declare.