Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia

BMC Cancer

Jerald P Radich⁸  Giuseppe Saglio⁴  Dong-Wook Kim⁹  Andreas Hochhaus⁵  Richard C Woodman³  Simona Soverini⁶  Susan Branford²  Enrico Gottardi⁴  Lan Beppu⁸  Martin C Müller¹  Timothy P Hughes²  Giovanni Martinelli⁶  Andrew M Stein⁷ 

[1]Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany

[2]Centre for Cancer Biology/SA Pathology, Royal Adelaide Hospital, Adelaide, Australia

[3]Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

[4]University of Turin, Orbassano, Italy

[5]Universitätsklinikum Jena, Jena, Germany

[6]University of Bologna, Department of Hematology and Oncological Sciences “L. e A. Seràgnoli, Bologna, Italy

[7]Novartis Institutes for BioMedical Research, Inc., 45 Sidney St, Cambridge, MA 02139, USA

[8]Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

[9]Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea

关键词: Molecular response;    BCR-ABL;    Mathematical modeling;    Nilotinib;    Chronic myeloid leukemia;   

Others  :  1079817
DOI  :  10.1186/1471-2407-13-173

 received in 2012-08-23, accepted in 2013-01-31,  发布年份 2013

【 摘 要 】

Background

We evaluated BCR-ABL1 kinetics in patients treated with nilotinib and analyzed whether a dynamic model of changes in BCR-ABL1 levels over time could be used to predict long-term responses.

Methods

Patients from the nilotinib registration trial (CAMN107A2101; registered at http://www.clinicaltrials.gov webcite as NCT00109707) who had imatinib-resistant or -intolerant Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase with BCR-ABL1 > 10% (on the international scale [IS]) at baseline and, in the first 6 months, had at least three BCR-ABL1 transcript measurements and an average daily dose of at least 720 mg were included in this analysis (N = 123).

Results

More than half of patients (65/123; 53%) had a slow monophasic response and the remainder (58/123; 47%) had a biphasic response, in which patients had a rapid initial decrease in BCR-ABL1 transcripts followed by a more gradual response. The biphasic response type strongly correlated with improved event-free survival (EFS). Data in the first 6 months of follow-up were sufficient to predict EFS at 24 months.

Conclusions

Unlike newly diagnosed patients with Ph+ CML-CP—in whom the majority had a biphasic response—approximately half of patients with imatinib-resistant or -intolerant CML had a slower, monophasic response. Second-line patients who did have a biphasic response had an EFS outlook similar to that of newly diagnosed patients treated with imatinib. Our model was comparable to using BCR-ABL1 (IS) ≤ 10% at 6 months as a threshold for predicting EFS.

【 授权许可】

   
2013 Stein et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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