CML-337 Therapeutic Results of Second-Generation TKIs in a CML Multicentric Study in the West Region of Algeria

Abstract

Historically, treatments for chronic myeloid leukemia (CML) are palliative, except for bone marrow allograft. Despite the results obtained using imatinib, a first-generation tyrosine kinase inhibitor (TKI), some patients (pts) have weak responses. The second-generation TKIs dasatinib and nilotinib are therapeutic alternatives in pts resistant to imatinib. This retrospective, multicenter study included 7 hematology centers in western Algeria. Pts older than 15 years treated with dasatinib or nilotinib as second-line therapy were included. The analysis of prognostic factors and the study of therapeutic responses were conducted according to ELN 2013. Event-free survival, progression-free survival, and overall survival (OS) were calculated according to the Kaplan-Meier method. Between January 2007 and December 2018, we collected 494 pts with CML, 154 of whom were treated with second-generation TKIs at a median age of 45 years (16, 83). The sex ratio was 0.87. The average splenic overflow was 8 cm. The average leukocytosis was 100 Giga/L. The average hemoglobin level was 10 g/dl (5.5-15). The average platelet rate was 35.5 Giga/L (27-1120). The majority of pts (120, 80%) had intermediate or high Sokal scores. The myelocytic phase was detected in 132 pts (86%), accelerated phase in 19 pts (13%), and acute transformation phase in 1 pt (1%). The indication for second-generation TKI was pts in accelerated phase in 70% of cases, failure to respond to first-generation TKI in 25% of cases, and intolerance in 5% of cases. Dasatinib was used in 75 pts (50%), nilotinib in 44 pts (30%), and dasatinib then nilotinib in 33 pts (20%). Evaluable pts (154) included 61% in MMR and 39% in failure, 25 pts died, and 25 pts were lost to follow-up. Toxicity was primarily hematological and digestive. OS was 80% at 5 years. The results obtained in our series are encouraging because second-generation TKIs as second-line therapy allowed treatment of 62% of pts who were intolerant or failing to respond to imatinib with acceptable digestive and hematological toxicity.