Differences in hematological and non-hematological toxicity during treatment with imatinib in patients with early and late chronic phase chronic myeloid leukemia

Abstract

Imatinib is a relatively specific inhibitor of the BCR/ABL tyrosine kinase, effective in chronic myeloid leukemia (CML). The aim of our study was to analyse the frequency and type of hematological and non-hematological adverse events in our series of late and early chronic phase patients with CML treated with imatinib and correlate the grade of hematological toxicity with the response obtained. Hematological events were seen in 59 out of 150 (39%) late chronic phase (CP) patients: of these, 24% experienced toxicity Grade 3-4. Of the 100 early CP patients, 26 (26%) had hematological adverse event: 7% experienced toxicity Grade 3-4 (p=0.0001). We found that only in early CP patients, the occurrence of hematological side effects of any grade within 6 months of therapy had a negative influence on cytogenetic response. We compared the incidence of non-hematological adverse events occurring in late and in early CP patients and found that in these latter, some side effects were more frequent, such as weight gain, periorbital edema, muscle cramps, skin rashes, diarrhea, weeping. On the contrary, we found that bone pain and hemorrhagic events were more common in late CP patients. Grade 3-4 adverse events were recorded at rates below 4% and decreased over time: in late CP patients hemorrhages and muscle cramps were the most common side effects of Grade 3-4, whereas in early CP patients, the most frequent events were nausea, weight gain and cutaneous rash. We have observed that hematological and non-hematological side effects during imatinib therapy are different among late and early CP patients and that severe hematological toxicity may influence cytogenetic response only in early CP patients.

Non-hematological Adverse Events of Imatinib in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

“…Elderly female patients had higher Imatinib concentrations and more AEs (Gotta et al, 2014). There is reduction in the risk of non-hematological AEs with early treatment, including weight gain (11%), periorbital edema (12%), rash (9%), diarrhea (11%), and bone pain (8%) (Breccia et al, 2008). Common AEs of Imatinib were relatively similar and comparable to others.…”

Hematologic toxicities of small molecule tyrosine kinase inhibitors

“…One phase III trial compared 800 mg daily to 400 mg daily reported almost twice the incidence of grade 3 or 4 cytopenias in the higher dose group [13]. Breccia et al compared toxicities of patients treated in early or late (after failure of interferon) CP CML and found that grade 3 or 4 cytopenias were seen in 7% and 24% of patients respectively [14]. They also found shorter median duration of cytopenias in early CP CML (10-14 days) compared to LP CML (16-20 days).…”

Chronic myeloid leukemia treatment guidelines: Brazilian Association of Hematology, Hemotherapy and Cell Therapy. Brazilian Medical Association Guidelines Project - 2012

“…Early treatment reduces the risk of grade I and II adverse effects by 52% (NNT: 2) and grade III and IV adverse effects by 81% (NNT: 1), although it increases the risk of neutropenia and thrombocytopenia by 5% (NNH: 20). After one year of follow-up in patients who have not achieved complete cytogenetic response, early treatment produces a reduction in the risk of grade I adverse events by 3% (NNT: 33), grade II by 8% (NNT: 12) and grades III and IV by 7% (NNT: 14) (45) (B).…”

“…In early treatment, there is a 16% increase in complete cytogenetic response (NNT: 7), a 2% reduction in the risk of relapse (NNT: 50) and a 15% increase in disease-free survival (NNT: 7) (45) (B).…”

“…There is reduction in the risk of non-hematological adverse events with early treatment, including weight gain (11%), periorbital edema (12%), rash (9%), diarrhea (11%), and infections (19%), but there is increased risk of hemorrhage (5%) and bone pain (8%) (45) (B).…”