Real-life comparison of severe vascular events and other non-hematological complications in patients with chronic myeloid leukemia undergoing second-line nilotinib or dasatinib treatment

Abstract

We retrospectively analyzed the rates of significant non-hematological adverse events (AEs) in 105 patients with chronic myeloid leukemia (CML) treated with second-generation tyrosine kinase inhibitor (TKIs) dasatinib or nilotinib used as second-line therapy in Polish tertiary care centers. Our analysis revealed that in a "real life setting," nearly half of patients with CML on second-generation TKIs suffer from therapy complications. Grade 2-5 non-hematological AEs were observed in 40% of patients treated with nilotinib and in 42% treated with dasatinib (p=0.83). Severe vascular events including peripheral artery occlusive disease (PAOD) occurred in 11% of patients on nilotinib and 4% on dasatinib (p=0.16). Pleural effusion occurred more often in the dasatinib group (26%) than in the nilotinib group (2%) (p=0.003). Importantly, most AEs occurred late, after more than 1 year of treatment. Since AEs are most often the reason for poor therapy compliance, careful monitoring of tolerability is crucial for an optimal treatment response in CML.

Mortality and Vascular Events Among Elderly Patients With Chronic Myeloid Leukemia: A Retrospective Analysis of Linked SEER-Medicare Data

“…15 A retrospective study reported that 8% of patients with CML treated with dasatinib or nilotinib experienced VEs within 28 months. 16 In clinical trials of ponatinib, 8.9% of patients experienced serious arterial thrombotic events (including cardiovascular, cerebrovascular, and peripheral VEs) within 11 months, 17 and 30% experienced serious arterial occlusive event (including cardiovascular, cerebrovascular, peripheral vascular, and venous thromoembolic events) during a 4-year period. 18 A recent meta-analysis of 29 clinical studies reported an incidence rate for a composite of major arterial events (PAOD, ischemic heart disease, stroke, or transient ischemic attack) of 8 per 1000 patient-years for patients with CML not treated with TKI, 11 for those treated with dasatinib, 1 for those treated with imatinib, 4 for those treated with bosutinib, 28 for those treated with nilotinib, and 106 for those treated with ponatinib.…”

“…19 With the exception of a recent meta-analysis, very limited evidence is available for the risk of VEs in patients with CML unrelated to TKI treatment. [14][15][16] One recent retrospective study of Swedish patients with myeloproliferative neoplasms (MPNs) found a greater risk of death from cardiovascular disease for patients with MPN than for matched controls (hazard ratio [HR], 1.5-8.8, depending on the age group). 20 To the best of our knowledge, no similar studies specifically analyzing CML have been published.…”

Dasatinib and Dysfunction of Platelets

“…In general, 140 mg OD dose of dasatinib has a better usual side effect profile (e.g. pleural effusion) than 70 mg BD [4]. However, with reference to platelet dysfunction, Quintás-Cardama et al did not find any significant difference amongst different dose schedule of dasatinib [5].…”

Severe dyspnoea in a patient with chronic myelogenous leukaemia on a tyrosine kinase inhibitor

“…This case demonstrates that pleural complications of TKI can be severe and hinder treatment of CML. Almost half the number of patients with CML on second-generation TKIs experience side effects, including pleural effusion in 26% of patients on dasatinib and 2% on nilotinib 12. Side effects are often a reason for the difficulty patients have with adhering to these lifelong drugs 12.…”

“…Almost half the number of patients with CML on second-generation TKIs experience side effects, including pleural effusion in 26% of patients on dasatinib and 2% on nilotinib 12. Side effects are often a reason for the difficulty patients have with adhering to these lifelong drugs 12. Unfortunately, although there are multiple TKIs, there can be cross reactions between them regarding adverse effects.…”