Imatinib Provides Durable Molecular and Cytogenetic Responses in a Practical Setting for Both Newly Diagnosed and Previously Treated Chronic Myelogenous Leukemia: A Study in Nagasaki Prefecture, Japan

Abstract

To evaluate the efficacy of imatinib in a practical setting, we registered 43 patients with newly diagnosed chronic myelogenous leukemia (CML) (group I) and 56 patients with previously diagnosed CML (group II) at 11 hematology centers in Nagasaki prefecture, Japan, from December 2001 to July 2005 and analyzed the molecular responses. Cytopenia, fluid retention, and skin rash were major adverse events, along with elevation in creatine phosphokinase levels. With a follow-up of approximately 3.5 years, imatinib treatment led to 88.7% overall survival (OS) and 85.2% progression-free survival (PFS) rates for group I, and 79.8% OS and 76.6% PFS rates for group II; the rates were not significantly different despite a lower average imatinib dose in group II. The rates of complete cytogenetic response at 30 months and major molecular response at 24 months were 86.1% and 62.5%, respectively, in group I, and 77.9% and 58.3% in group II; the rates were not significantly different. As has been reported by other groups, these results demonstrate that imatinib treatment can provide excellent clinical and molecular effects for not only newly diagnosed but also previously treated CML patients in practical settings that cover a wider variety of patients than clinical trials.

Phase 1/2 clinical study of dasatinib in Japanese patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia

“…It has been reported that most Japanese CML patients are treated with lower dosages of imatinib than the standard recommended dosage, because of toxicities [28][29][30][31]. Imatinib treatment at low dosage is related with low rate of cytogenetic response [30].…”

Long-term efficacy of imatinib in a practical setting is correlated with imatinib trough concentration that is influenced by body size: a report by the Nagasaki CML Study Group

“…As shown in our previous report, the registration included approximately 85% of the patients in the Nagasaki-Prefecture Tumor Registry [7]. The 130 patients included 74 newly diagnosed patients from December 2001 to March 2008 and 56 patients who were alive in December 2001, at the beginning of the registration when imatinib became widely available in Japan.…”

“…Based on the results of several clinical trials including the IRIS study, imatinib administration (400 mg/day) has become the standard treatment for CML patients in chronic phase. We previously conducted an analysis of registered CML patients in Nagasaki prefecture of Japan capturing more than 80% of patients in this prefecture (approximate population of 1.44 million) to determine imatinib efficacy in a practical setting rather than in a clinical trial situation [7]. Reflecting the practical situation of daily clinic, clinical features of patients in our registration were different from those reported in the IRIS study in some aspects: older age, advanced Sokal score at diagnosis, and lower daily dose of imatinib administered in the Nagasaki Study.…”

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

“…A complete cytogenetic response (CCyR) rate of 60 to 67% and major molecular response (MMR) rate of 22 to 39% at 12 months have been reported for imatinib treatment [1][2][3][4][5][6]. A 6-year update of the IRIS study was recently presented, which revealed an event-free survival of 86% and overall survival of 88% [7].…”

“…Our previous cohort study with various patients (i.e. a group of patients in a practical setting) revealed that imatinib treatment could achieve excellent outcomes for CML patients, at both clinical and molecular levels [6].…”