Vol 2, Supp. B (2011)
Case report
Published online: 2012-02-28

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Nilotinib induced complete molecular response in the patient in chronic phase of chronic myeloid leukemia and imatinib intolerance after acetaminophen intake

Maria Lewandowska, Michał Gniot, Krzysztof Lewandowski

Abstract

Results of phase 2 and 3 clinical trials evaluating efficacy of imatinib (IM) in patients with chronic myeloid leukemia confirmed that frequency of grade 3 and 4 of liver toxicity does not exceed 5,1%. Usually, liver toxicity is associated with other intolerance symptoms like skin allergy. The time from IM therapy initiation to the occurrence of liver toxicity symptoms differs from 12 days to 18 months. In most of the cases repeated initiation of IM therapy resulted in reoccurrence of liver toxicity symptoms. In some patients liver toxicity symptoms occurrence is associated with acetaminophen administration. Recent results have shown that IM, in contrast to nilotinib, significantly inhibits UDP-glucoronidase dependent glucoronization of acetaminophen. Probably, both drugs also compete with transport mechanisms and P450 cytochrom dependent metabolic pathways. The paper presents treatment outcome of the patient treated with IM in whom therapy resulted in complete hematological response (CHR) and minor cytogenetic response achieved after 9 months of therapy, and liver toxicity symptoms occurrence after acetaminophen administration. Reintroduction of IM resulted in significant increase of aminotransferase activity in the blood after few days of the treatment. Due to persistent IM hepatotoxicity, nilotinib therapy in a dose of twice 400 mg daily was initiated. Therapy allowed us to obtain again CHR after one month, complete cytogenetic response after 3 months of the treatment, and complete molecular response after additional 8 months of the therapy. The presented case confirmed a good nilotinib tolerance and efficacy in patients with previous IM hepatotoxicity symptoms after acetaminophen intake.

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Hematology in Clinical Practice