Long-Term Outcome to First-Line Imatinib according to 2013 European LeukemiaNet Response Criteria: a GIMEMA CML WP Analysis

Despite other TKIs have been approved for frontline CML treatment, imatinib (IM) is an important therapeutic option. Response criteria at given time points have been proposed by the ELN panel, irrespectively of the first-line TKI used, to decide when the treatment should be continued, optimal response (OR), or changed, failure (F); warning (W) is an intermediate zone. To investigate the significance of 2013 ELN response criteria in CML treated frontline with IM, 559 patients enrolled within 3 prospective studies (CML021-022-023) were analyzed (ITT population of each study). ELN criteria at 3 months: not fully evaluable due to missing cytogenetic analysis in 452/559 patients; we focused on the early molecular response (EMR, BCR-ABL <10% at 3 months, corresponding to OR). ELN criteria at 6 and 12 months: F, BCR-ABL >10% and/or Ph+ >35% at 6 months, BCR-ABL >1% and/or Ph+ >0 at 12 months; OR, BCR-ABL <1% and/or Ph+ 0 at 6 months, BCR-ABL <0.1% at 12 months; W: intermediate conditions. Progression: according to 2013 ELN criteria. Molecular response: according to 2015 EUTOS recommendations. Leukemia-unrelated death (LRD): known cause of death, no progression, CCyR or MMR <6 months prior to death; all other deaths were classified as leukemia-related. Median follow-up, 76 (66-99) months. The EMR rate was 82%. The progression-free survival (PFS) and the probability of LRD according to the presence-absence of EMR were 91%-87% (p=0.035) and 11%-5% (p=0.019), respectively. Combining Sokal score and EMR, the patients were divided into 4 groups, LR-IR resp, LR-IR not resp, HR resp, HR not resp: the probability of LRD was 3%-9%-10%-20% (p<0.001). The patients remaining on IM according to the response at 6 months (OR-W-F) were 77%-52%-26%, respectively. The PFS and the probability of LRD according to ELN response at 6 months (OR-W-F) were 93%-92%-77% (p<0.001) and 2%-5%-28% (p<0.001), respectively. The patients remaining on IM according to the response at 12 months (OR-W-F) were 80%-72%-35%, respectively. The PFS and the probability of LRD according to ELN response criteria at 12 months (OR-W-F) were 95%-96%-85% (p<0.001) and 1%-1%- 16% (p<0.001), respectively. Patients without OR at 3 months (particularly high risk patients) had poorer outcome compared to patients with OR. Patients classified as W at 6 and 12 months have similar outcome to OR patients, both significantly better than F. The subsequent treatment may explain, at least in part, the absence of differences

Efficacy and safety of low-dose aspirin in polycythemia vera

BACKGROUND: The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial. METHODS: We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years. RESULTS: Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). CONCLUSIONS: Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment