Abstract
Introduction: Imatinib(IM) remains first-line treatment of choice in chronic myeloid leukemia (CML). Although nearly half of patients(pts) failure IM therapy, long-term survival is very high. It seems that this is due to the efficiency of subsequent treatment with new tyrosine kinase inhibitors (TKIs). We evaluate real long-term outcome of IM therapy when new TKIs are unavailable and mainly generic forms of IM are provided.
Methods: All 63 pts (male-24, female-39) in chronic phase (CP) CML treated with IM in Gomel (Belorus) were included in the study. The pts never obtained new TKIs(not reimbursed) or allogeneic stem cell transplantation. Median age at the time of IM treatment start was 52 (range 18-71) years in whole group, 48 and 53years in men and in women respectively. IM was given within 3 months after diagnosis in 33 (52%) pts. Median CML duration before IM treatment for other group was 25,7 (range 4-136) months. The Sokal score distribution was low, intermediate and high in 54 (86%), 5 (8%) and 4(6%) cases respectively.
Results: Median duration of IM therapy was 31 (2-135) months. It was 26 (range 5-83) and 37(range 2-135) months respectively in pts started IM within 3 months after CML or later. The reasons of IM discontinuation were toxicity(n=4) and resistance(n=15). During observational time 17(27%) pts progressed to accelerated (AP) or blastic phase (BP). Median time from IM to AP/BP was 9 (range 0,5-60) months. Pts with longer CML duration before IM were at higher risk for progression. Thus, median time from CML to IM started was 22 months and only 1 month in pts with and without progression to AP/BP. During observation 14 (22%) pts died. Progression was the main reason for death (n=12). Median time of ovecvrall survival was 31 (range 7-135) months. 5- and 8 year of (OS) probability for all pts were 78% and 60% respectively. 5-year survival probability was higher in pts started IM shortly after CML (see in figure 1). Complete cytogenetic response (CCyR) was obtained in 30(63%) of ots. Clinical outcome according to the time from CML to IM see in table 1. Only 1/30(3,3%) pt with and 13/32 (40%) pts without CCyR died during observation. The majority of pts had low Sokal score, so we couldn't analyze influence of Sokal scores on IM efficacy. IM therapy was discontinued in 18(30%) of pts. The reasons of IM discontinuation were toxicity(n=4) and resistance(n=15). 5 pts are still alive on interferon or different chemotherapy. The median time of observation after IM discontinuation was 2,5 (range 0,5-27) months.
Conclusions: IM (mainly generics) therapy was effective in the most CP CML pts. Early onset of IM therapy and the achievement of CCyR were associated with an improved survival. When we compared the date on IM therapy to other clinical trials it seems that the cumulative rate of CCyR is lower in spite of the most pts were with low Sokal score. The study is nonrandomized retrospective, so it is impossible to claim that this is related to the use of IM generics. Meanwhile IM mono therapy as first line may provide low rate of AP/BC and high OS probability, although long-term clinical outcome definitely worse compared to studies, where new TKIs are available. To the best of our knowledge, this is the first, study of CML treatment by IM (generics) without second generation drugs.
Clinical outcome on IM therapy in CP CML pts according to the time from CML to IM.
Survival probability in CP CML pts started IM within or outside 3 months after CML diagnosis
Survival probability in CP CML pts started IM within or outside 3 months after CML diagnosis
Zaritskey:Janssen: Consultancy; Novartis: Consultancy.
