Clinical Experience and Perspectives of Bosutinib Use in Patients with Chronic Myeloid Leukemia

NOVEL DRUGS , , , ,

VA Shuvaev1, OYu Vinogradova2,3,4, IS Martynkevich1, NV Novitskaya2, MS Fominykh1, SN Tsareva2, DI Shikhbabaeva2, MM Pankrashkina2,3, MV Chernikov2, NN Sharkunov2, II Zotova1, VYu Udal’eva1, EV Motyko1, SV Voloshin1,5,6

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2 SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

3 Dmitrii Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117198

4 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

5 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

6 II Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 191015

For correspondence: Ol’ga Yur’evna Vinogradova, MD, PhD, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284; Tel.: +7(495)945-97-61; e-mail: olgavinz@mail.ru.

For citation: Shuvaev VA, Vinogradova OYu, Martynkevich IS, et al. Clinical Experience and Perspectives of Bosutinib Use in Patients with Chronic Myeloid Leukemia. Clinical oncohematology. 2018;11(4):288–94.

DOI: 10.21320/2500-2139-2018-11-4-288-294

ABSTRACT

Aim. To evaluate the clinical experience of bosutinib use for treatment of chronic myeloid leukemia (CML) patients with intolerance and resistance to other tyrosine kinase inhibitors (TKI), as well as to compare the obtained results with the data of clinical trials.

Materials & Methods. The analysis was conducted on case history records of 51 CML patients (25 men and 26 women; median age was 56 years, range 28–86). By the beginning of bosutinib therapy 37 chronic phase, 8 acceleration phase, and 6 blast crisis patients were included in the study. Bosutinib was administered as second–line TKI treatment in 10 patients, as third–line treatment in 18 patients, and as fourth–line treatment in 23 patients. The causes for switching to bosutinib were poor tolerance of previous TKI therapy in 21 patients and resistance to previous TKI therapy in 30 patients.

Results. The median duration of bosutinib treatment was 6 months (range 1–50). Bosutinib toxicity profile and its tolerance in common clinical practice corresponded to the data of clinical trials. Because of adverse events the therapy was discontinued only in 5 (10 %) patients. Complete hematological response was 88 % (persistent response was maintained in 76 % of patients); complete cytogenetic response (CCyR) was 39 %, (persistent response in 37 % of cases); major molecular response (MMR) was 31 % (it was confirmed in 25 % of patients during the last follow-up visit). The efficacy of bosutinib in the real clinical setting was slightly higher compared to the results of clinical trials. This difference was associated with a disease phase, a reason for withdrawal of the previous TKI, line of treatment, BCR–ABL mutations, and the form of them. The therapy was continued in 22 (43 %) patients, most of them reached stable optimal response, both CCyR and MMR.

Conclusion. Bosutinib appears to be an acceptable alternative to other TKIs having its specific mechanisms of action and adverse events. The efficacy and safety of bosutinib proved in routine clinical practice are sufficient to recommend it for use in national hematology.

Keywords: chronic myeloid leukemia, bosutinib, target therapy, tyrosine kinase inhibitors, clinical practice.

Received: May 9, 2018

Accepted: August 10, 2018

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