bosutinib

Management of Chronic Myeloid Leukemia Patients During Pregnancy (Analysis of Literature and Practical Recommendations)

MYELOID TUMORS , , , , ,

EYu Chelysheva1, AG Turkina1, ES Polushkina2, MA Vinogradova2, RG Shmakov2

1 National Medical Hematology Research Center, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina str., Moscow, Russian Federation, 117997

For correspondence: Ekaterina Yur’evna Chelysheva, MD, PhD, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-48-60; e-mail: denve@bk.ru

For citation: Chelysheva EYu, Turkina AG, Polushkina ES, et al. Management of Chronic Myeloid Leukemia Patients During Pregnancy (Analysis of Literature and Clinical Experience). Clinical oncohematology. 2019;12(2):202–10.

DOI: 10.21320/2500-2139-2019-12-2-202-210

ABSTRACT

Background. The tyrosine kinase inhibitors (TKI) era is marked by a long-term favorable prognosis of chronic myeloid leukemia (CML). In this context CML patients of reproductive age are faced with major issues of family planning with due regard to the risk of TKI treatment interruption during pregnancy. Additionally, TKI impact is another potential risk to the fetus.

Aim. To develop differentiated approach to CML treatment during pregnancy.

Materials & Methods. Analysis includes literature data and clinical experience based on 166 pregnancies of 120 CML patients from CML Pregnancy Registry.

Results. Pregnancy planning is recommended after achieving stable and deep molecular response (with BCR-ABL > 0.01 %, IS) within the period of at least 2 years. At conception TKI therapy does not have to be interrupted. However, early pregnancy detection and TKI treatment interruption after pregnancy confirmation are of vital importance due to teratogenic risks. Furthermore, no TKI may be administered during organogenetic period, i.e. up to the 15th week of gestation. In the absence or loss of complete hematologic response and growth of BCR-ABL > 1 % after the 15th week of gestation imatinib or nilotinib administration is justified in the interest of pregnant patients taking into account limited transfer of these drugs through placenta. In the absence of complete hematologic response before the 15th week of gestation interferon-α can be administered. With BCR-ABL < 1 % patients can be either followed-up without therapy or they can receive interferon-α throughout pregnancy. Dasatinib, bosutinib, and other TKI are contraindicated at any stage of pregnancy. There are no special recommendations for childbirth, delivery is to be adapted to obstetric conditions. Breast feeding is not recommended because of the lack of practical evidence for its safety.

Conclusion. A regular molecular monitoring of BCR-ABL and hematologic status is indispensable, health condition of fetus should be continuously monitored as well. CML patient management should be conducted by cooperating hematologists and gynecologists.

Keywords: chronic myeloid leukemia, pregnancy, tyrosine kinase inhibitors, imatinib, nilotinib, dasatinib, bosutinib.

Received: January 9, 2019

Accepted: March 20, 2019

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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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