tyrosine kinase inhibitors

Chronic Myeloid Leukemia Patient Registry in the Russian Federation: From Observational Studies to the Efficacy Evaluation in Clinical Practice

MYELOID TUMORS , , ,

AG Turkina1, NV Novitskaya2, AK Golenkov3, VA Shuvaev4, LI Napso5, IV Krylova6, AM Savrilova7, GSh Safuanova8, AV Korobkin9, TYu Klitochenko10, EV Burnasheva11, EV Vasil’ev12, OM Senderova13, EYu Fedorova14, LM Yalunina15, EK Nekhai16, GB Kuchma17, AS Lyamkina18, NG Shchedrova19

1 Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

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

3 NF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina str., Moscow, Russian Federation, 129110

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

5 Clinical Oncology Dispensary No. 1, 146 Dimitrova str., Krasnodar, Russian Federation, 350040

6 Sverdlovsk Regional Clinical Hospital No. 1, 185 Volgogradskaya str., Ekaterinburg, Russian Federation, 620102

7 Republican Clinical Hospital, 138 Orenburgskii trakt, Kazan’, Russian Federation, 420064

8 GG Kuvatov Republican Clinical Hospital, 132 Dostoevskogo str., Ufa, Russian Federation, 450005

9 Chelyabinsk Regional Clinical Hospital, 70 Vorovskogo str., Chelyabinsk, Russian Federation, 454076

10 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

11 Rostov State Medical University, 29 Nakhichevanskii per., Rostov-na-Donu, Russian Federation, 344022

12 Regional Clinical Hospital, 3A Partizana Zheleznyaka str., Krasnoyarsk, Russian Federation, 660022

13 Irkutsk Order of the Badge of Honor District Clinical Hospital, 100 Yubileinyi microdistrict, Irkutsk, Russian Federation, 664049

14 VD Seredavin Samara Regional Clinical Hospital, 159 Tashkentskaya str., Samara, Russian Federation, 443095

15 SV Belyaev Kemerovo Regional Clinical Hospital, 22 Oktyabr’skii pr-t, Kemerovo, Russian Federation, 650066

16 Regional Clinical Hospital No. 2, 55 Russkaya str., Vladivostok, Russian Federation, 690105

17 Orenburg Regional Clinical Hospital No. 1, 5/3 Tsvillinga str., Orenburg, Russian Federation, 460006

18 Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

19 Novartis Pharma, 72 bld. 3, Leningradskii pr-t, Moscow, Russian Federation, 125315

For correspondence: Anna Grigor’evna Turkina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: turkianna@yandex.ru

For citation: Turkina AG, Novitskaya NV, Golenkov AK, et al. Chronic Myeloid Leukemia Patient Registry in the Russian Federation: From Observational Studies to the Efficacy Evaluation in Clinical Practice. Clinical oncohematology. 2017;10(3):390–401 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-390-401

ABSTRACT

Background. Due to the significant increase in life expectancy and the quality of life in patients with chronic myeloid leukemia (CML) as well as the growing need for expensive tyrosine kinase inhibitors (TKI), the analysis of cost-effectiveness and lifelong monitoring of patients is especially important.

Aim. We present the results of a multicenter observational study “The Russian Registry of Chronic Myeloid Leukemia in routine clinical practice (2011–2016)”.

Materials & Methods. The study included Russian patients with CML, confirmed by the detection of a Ph-chromosome or a BCR-ABL transcript. The statistical analysis (July 1, 2016) included 7609 patients from 80 regions of the Russian Federation (covering 95 % of the population). The annual increase in the number of patients with newly diagnosed CML was 600–650 patients. At the time of the statistical analysis, 6995 (92 %) patients remained under observation, 473 (6 %) died and 141 (2 %) were withdrawn. The registry included 44 % of men and 56 % of women, the median age was 49 years (range 2–94 years). The peak incidence (46.3 %) occurred at the age of 40–60 years. The median disease duration by the time of the analysis was 6 years (range 0.1–30 years).

Results. The disease was diagnosed in the chronic phase (CP), acceleration phase, and blast crisis in 6560 (93.8 %), 380 (5.5 %) and 47 (0.7 %) patients, respectively. The proportion of risk groups according to Sokal for low, intermediate and high risk in CP was 49 %, 30 %, and 21 %, respectively. TKI were administered to 6473 (92.5 %) patients. Imatinib and the second generation TKI (TKI2) were administered to 5570 (86 %) and 903 (14 %) patients, respectively. The total of 30.4 % of patients received the increased imatinib dose of 600–800 mg. In the TKI2 group, 558 (61.7 %) patients received nilotinib and 345 (38.2 %) patients received dasatinib. The proportion of patients with completed molecular genetic studies (MGS) in 2014, 2015 and the first 6 months of 2016 amounted to 61 %, 58 % and 23 %, respectively. The proportion of patients with cytogenetic studies (CS) for the same period was 28 %, 26 % and 7 %, respectively. No CS or MGS data were presented for 34 %, 35 % and 63 % of patients during this period. Optimal molecular response and major molecular response (MMR) for TKI therapy were observed in 23 % and 58 % of patients treated < 12 months and > 12 months, respectively. When nilotinib was used in the second line, MMR was obtained in 42 % of patients, and a deep molecular response was obtained in 25 % of patients (BCR-ABL < 0.01 %).

Conclusion. The high efficacy of TKI therapy was observed in the majority of patients with the possibility of achieving a minimal residual disease. The problems concerning untimely monitoring and suboptimal administration of second line treatment were identified. In general, the CML patient registry allowed the data integration of data and information management of population with CML in Russia.

Keywords: chronic myeloid leukemia, registry, tyrosine kinase inhibitors, imatinib, nilotinib, quality of medical care.

Received: January 17, 2017

Accepted: April 27, 2017

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Clinical Recommendations for the Diagnosis and Treatment of Chronic Myeloid Leukemia

CLINICAL GUIDELINES ,

GROUP OF AUTHORS UNDER THE SUPERVISION OF ACADEMICIAN VG SAVCHENKO

AG Turkina1, AYu Zaritskii2, VA Shuvaev3, EYu Chelysheva1, EG Lomaia2, EV Morozova4, AK Golenkov5, TI Pospelova6, OA Shukhov1, MS Fominykh3, GA Gusarova1, LA Kuz’mina1, AO Abdullaev1, IS Martynkevich3

1 Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 Federal Almazov North-West Medical Research Centre, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

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

4 RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

5 NF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina str., Moscow, Russian Federation, 129110

6 Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

For correspondence: Anna Grigor’evna Turkina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: turkianna@yandex.ru

For citation: Turkina AG, Zaritskii AYu, Shuvaev VA, et al. Clinical Recommendations for the Diagnosis and Treatment of Chronic Myeloid Leukemia. Clinical oncohematology. 2017;10(3):294–316 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-294-316

ABSTRACT

This article is the 4th edition of the recommendations for the diagnosis and treatment of chronic myeloid leukemia. The group of authors reviewed and discussed relevant new publications, and included the significant remarks and comments of experts. Particular attention was paid to the control of risk factors for the development of arterial vascular events and their prevention, and adverse effects of the long-term therapy with tyrosine kinase inhibitors, which were being increasingly reported in recent years.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, molecular response, vascular complications, therapy algorithm.

Received: November 15, 2016

Accepted: February 19, 2017

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Arterial Events in Patients with Chronic Myeloid Leukemia Receiving Treatment with Second Generation Tyrosine Kinase Inhibitors

COMPLICATIONS OF ANTITUMOR TREATMENT , , ,

GA Gusarova, AG Turkina

Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Galina Anatol’evna Gusarova, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel: +7(495)612-16-36; e-mail: galina1966@bk.ru

For citation: Gusarova GA, Turkina AG. Arterial Events in Patients with Chronic Myeloid Leukemia Receiving Treatment with Second Generation Tyrosine Kinase Inhibitors. Clinical oncohematology. 2016;9(4):474–84 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-474-484

ABSTRACT

Target therapy of chronic myeloid leukemia (CML) by tyrosine kinase inhibitors (TKI) allows to achieve high rates of the overall survival in CML. The choice of TKI treatment in every particular case should be based on individual CML patient’s characteristics, including comorbidities and the risk of adverse events (AE). Every TKI has a particular toxicity profile depending on off-target action spectrum. A probability of arterial AEs on TKI therapy is comparatively low but they may be life threatening. It is highly important to evaluate this kind of AEs during a long period of vascular TKI exposure. The age-specific increased incidence of cardiovascular and respiratory diseases is an additional factor in these patients with high overall survival on TKI therapy. The article is devoted to the analysis of frequency, mechanisms, particular features, methods of diagnostics and treatment of arterial AEs emerging on second generation TKI (nilotinib and dasatinib) therapy. The detailed characteristics of arterial occlusive events on nilotinib therapy and pulmonary arterial hypertension on dasatinib are presented. Special attention is paid to the analysis of risk factors of vascular AEs and the ways to correct modified risk factors. Timely assessment of clinical symptoms of cardiopulmonary, ischemic diseases/complications, and metabolic disorders helps to find specialized medical care (by a cardiologist, pulmonologist, endocrinologist), to prescribe an adequate therapy, provide prevention of complications and make decision about TKI dose adjustment/switching to alternative TKI being a true foundation of safe personalized treatment in CML patients.

Keywords: tyrosine kinase inhibitors, artery occlusion, atherosclerosis, pulmonary hypertension.

Received: May 24, 2016

Accepted: June 16, 2016

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Chronic Myeloid Leukemia: Long-Term Experience of Target Therapy

MYELOID TUMORS , , , ,

KM Abdulkadyrov, VA Shuvaev, IS Martynkevich, MS Fominykh, NA Potikhonova, II Zotova, VYu Udal’eva, RA Golovchenko, NV Shakhvorostova, DI Shikhbabaeva, MN Zenina, SA Tiranova, SA Kudryashova, LS Martynenko, MP Ivanova, NYu Tsybakova, EV Petrova, LB Polushkina, EV Kleina

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

For correspondence: Vasilii Anatol’evich Shuvaev, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)636-54-72; e-mail: shuvaev77@mail.ru

For citation: Abdulkadyrov KM, Shuvaev VA, Martynkevich IS, et al. Chronic Myeloid Leukemia: Long-Term Experience of Target Therapy. Clinical oncohematology. 2016;9(1):54–60 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-54-60

ABSTRACT

Background & Aims. Interpretation of key aspects of pathogenesis of chronic myeloid leukemia (CML) and development and introduction of target therapy have changed the prognosis of this once fatal disease dramatically. Results of numerous clinical trials demonstrated substantial superiority of tyrosine kinase inhibitors over previous therapy techniques. At the same time, clinical trials had limitations in patient enrollment, as well as treatment conditions and duration. The analysis of our clinical experience in CML target therapy (over the period from 2003 till 2015) is an important argument for introduction of novel drugs into routine clinical practice. The aim of the study is to analyze our own experience in CML target therapy and to compare our results with clinical trials data.

Methods. Outpatient’s cards and case histories of CML patients treated in the Russian Scientific Research Institute of Hematology and Transfusiology over last 12 years were analyzed in this work. Published results of multi-center clinical trials evaluating the use of tyrosine kinase inhibitors in CML were used for a comparative analysis. The primary morbidity rate and the prevalence of CML, results of first and subsequent treatment lines were studied with assessment of survival rates, adverse events, and the nature of the response (hematologic, cytogenetic and molecular).

Results. The experience in treatment of 208 CML patients was analyzed. The use of imatinib led to clinical and hematological remission (complete hematologic response) was achieved in 95 % of patients. The frequency of complete cytogenetic responses (CCyR) was 69 %, and that of major molecular responses (MMR) was 58 %. The overall 5-year survival (OS) was 86.4 %, the 10-years OS was 67.5 %. The use of nilotinib during the second line permitted to achieve CCyR in 61 % of patients, and the MMR in 55 % of cases. The two-year OS was 96 % and the 5-year OS was 68 %. CCyR and MMR were achieved in 50 % patients treated with dasatinib during the second line. As for the third line, CCyR was achieved in 50 % of patients and MMR in 25 %. In case of previous imatinib and nilotinib resistance, CCyR was observed only in 36 % of patients and MMR in 18 % of cases. During second-line dasatinib treatment, the 2-year OS was 85 %, and the 5-year OS was 51 %; as for the third line, the results were 75 % and 50 %, respectively. The range and rates of adverse events of the therapy, in general, corresponded to results of clinical trials.

Conclusion. The use of tyrosine kinase inhibitors in treatment of CML permits to prolong patient’s life span and quality of life significantly. The use of nilotinib and dazatinib (in case of nilotinib intolerance and/or resistance) could be effective in most patients.

Keywords: chronic myeloid leukemia, target therapy, tyrosine kinase inhibitors, imatinib, nilotinib, dasatinib, clinical practice.

Received: September 10, 2015

Accepted: October 20, 2015

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First Line Treatment Choice for Chronic Myelogenous Leukemia: Modeling of Clinical and Economic Factors

MYELOID TUMORS , , , ,

VA Shuvaev, KM Abdulkadyrov, IS Martynkevich, MS Fominykh

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

For correspondence: Vasilii Anatol’evich Shuvaev, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)636-54-72; e-mail: shuvaev77@mail.ru

For citation: Shuvaev VA, Abdulkadyrov KM, Martynkevich IS, Fominykh MS. First Line Treatment Choice for Chronic Myelogenous Leukemia: Modeling of Clinical and Economic Factors.. Clinical oncohematology. 2015;8(1):78–83 (In Russ).

ABSTRACT

Background. Second generation tyrosine kinase inhibitors (nilotinib and dasatinib) have advantages over imatinib in frequency and rate of cytogenetic and molecular responses obtaining in chronic myelogenous leukemia (CML) treatment. At the same time, they produced more severe adverse effects and are more expensive than imatinib. At present, CML patients with stable deep molecular response are considered as candidates for enrollment into clinical trials studying the management of treatment-free remission. Constant growth of expenses for CML diagnosing and treatment require a pharmacoeconomic analysis in order to optimize expenses and provide cost-effectiveness data for introduction of novel highly effective drugs.

Objective. Pharmacoeconomic modeling of the choice of CML treatment using first and second generation tyrosine kinase inhibitors in first-line therapy with an analysis of sensitivity of clinico-economic factors.

Methods. Pharmacoeconomic modeling of CML diagnosing and treatment. Cost-utility analysis of first and second generation tyrosine kinase inhibitors in first-line treatment. Sensitivity analysis with identification of most important clinical and economic factors affecting treatment results. Simulation for feasibility analysis of the nationwide use of first and second generation tyrosine kinase inhibitors in first-line therapy.

Results. Sensitivity analyses of pharmacoeconomic models showed its robustness. The threshold limits for drug costs and frequency of achievement of a complete molecular response affecting economic feasibility of the choice of first and second generation tyrosine kinase inhibitors were determined.

Conclusions. These pharmacoeconomic models may be applied for improvement of diagnostic and therapeutic standards.

Keywords: chronic myeloleukemia, tyrosine kinase inhibitors, imatinib, nilotinib, dasatinib, pharmacoeconomics, cost-effectiveness.

Received: September 11, 2014

Accepted: November 7, 2014

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Second Generation Tyrosine Kinase Inhibitors and Their Toxicity in Treatment of Patients in Chronic Phase of Chronic Myeloid Leukemia

MYELOID TUMORS , ,

N.S. Lazorko1, E.G. Lomaia1, E.G. Romanova1, E.I. Sbityakova1, E.R. Machyulaitene2, P.A. Butylin1,3, A.Yu. Zaritskii1,2

1 Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russia, 197341

2 Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russia, 197022

3 Saint Petersburg State University of Information Technologies, Mechanics and Optics, Institute of Translational Medicine, 49 Kronverkskii pr-t, Saint Petersburg, Russia, 197101

For correspondence: Elza Galaktionovna Lomaia, PhD, 2 Akkuratova str., Saint Petersburg, Russia, 197341; Tel.: +7(812)702-37-65; e-mail: lomelza@gmail.com

For citation: Lazorko N.S., Lomaia E.G., Romanova E.G., Sbityakova E.I., Machyulaitene E.R., Butylin P.A., Zaritskii A.Yu. Second Generation Tyrosine Kinase Inhibitors and Their Toxicity in Treatment of Patients in Chronic Phase of Chronic Myeloid Leukemia. Klin. Onkogematol. 2015;8(3):302–8. (In Russ.)

ABSTRACT

Background & Aims. Certain experience in the use of new tyrosine kinase inhibitors (TKIs) in treatment of patients with chronic myeloid leukemia has been obtained over the last years. The article summarizes literature data on toxicity obtained in international clinical trials. The aim of the study is to evaluate adverse effects of second generation TKIs in the routine clinical practice and to assess their effect on patient future life.

Methods. We analyzed our own data obtained during routine clinical practice. 76 patients (36 men and 40 women) over 18 years of age (median age was 49 years, range 26–75) with chronic myeloid leukemia were enrolled in the retrospective trial. 48 patients were treated with nilotinib, 28 patients received dazatinib during the chronic phase of the disease as a second line therapy after withdrawal of imatinib mesylate. The toxicity degree was determined according to CTCAE 4.0 criteria.

Results. III–IV degree hematologic toxicity was registered in 36.8 % of patients. No significant difference in the incidence of complications between nilotinib and dazatinib groups was observed: 39.6 % and 32.1 %, respectively. II–IV degree non-hematologic toxicity was found in 35.4 % patients on nilotinib and in 25 % of patients on dazatinib. The incidence of individual types of toxicity did not exceed 15 %. A combination of different types of non-hematologic toxicity was observed in 9.2 % of patients. No TKI2 toxicity-related lethal outcomes were registered.

Conclusion. Hematologic and/or non-hematologic toxicity related to TKI2 was registered in more than 50 % of patients. In most cases, the complications were transient and eliminated after discontinuation of TKI2 or after dose reduction. TKI2-associated complications did not affect the possibility to achieve a complete cytogenetic response and its stability.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, toxicity.

Received: January 29, 2015

Accepted: June 1, 2015

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Imatinib Generics: Myths and Reality (Literature Review and Our Experience)

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF MYELOID MALIGNANCIES , , , ,

K.M. Abdulkadyrov, V.A. Shuvaev, M.S. Fominykh

Russian Research Institution of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

For citation: Abdulkadyrov K.M., Shuvaev V.A., Fominykh M.S. Imatinib Generics: Myths and Reality (Literature Review and Our Experience). Klin. onkogematol. 2014; 7(3): 311–6 (In Russ.).

ABSTRACT

The article describes the registration process of generic drugs in the Russian Federation. The article presents literature data and results of our own studies of the use of imatinib generics — PhilachromineÒ and GenfatinibÒ — in patients with chronic myelogenous leukemia. The tolerability (incidence of adverse events) and therapeutic efficacy (the number of optimal responses to therapy) were analyzed in comparison with historical control of patients, treated with GlivecÒ. 14 patients with chronic myeloleukemia treated with Philachromine® as a first-line treatment and 81 patients previously treated with GlivecÒ (54 of them received PhilachromineÒ and 27 patients received GenfatinibÒ) were included in study. Therapeutic efficacy and tolerability of generics (PhilachromineÒ and GenfatinibÒ) were similar to those of GlivecÒ within the compared observation period.

Keywords: chronic myeloleukemia, tyrosine kinase inhibitors, imatinib, generics, generic substitution, biological efficacy.

Address correspondence to: shuvaev77@mail.ru

Accepted: May 21, 2014

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REFERENCES

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Role of tyrosine-kinase inhibitor selectivity in development of adverse effects during treatment of chronic myeloid leukemia

REVIEWS , , ,

A.A. Zeifman1,2, E.Yu. Chelysheva3, A.G. Tukrina3, and G.G. Chilov1,2

1 N.D. Zelinsky Institute of Organic Chemistry, RAS, Moscow, Russian Federation

2 Fusion Pharma LLC, Moscow, Russian Federation

3 Hematology Research Center, RF MH, Moscow, Russian Federation

ABSTRACT

This review focuses on association between the selectivity of Bcr-Abl kinase inhibitors and the spectrum of their adverse effects during treatment of patients with chronic myeloid leukemia. The data on the structure and natural biochemical functions of the well-known adverse targets for inhibitors of Bcr-Abl kinases, including BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, and VEGFR1/2/3 are summarized, and the potential association between their off-target inhibition and adverse effects of tyrosine-kinase inhibitors is suggested.

Keywords: chronic myeloid leukemia, tyrosine-kinase inhibitors, selectivity, imatinib, nilotinib, dasatinib, ponatinib, PF-114, BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3.

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  108. Лазарева О.В., Костина И.Э., Туркина А.Г. Лекарственно-индуци- рованный пневмонит: редкое осложнение терапии иматиниба мезилатом у больных хроническим миелолейкозом. Клин. онкогематол. 2010; 3(1): 47–52.  [Lazareva O.V., Kostina I.Ye., Turkina A.G. Drug-induced pneumonitis: rare complication of imatinib mesylate therapy in patients with chronic myeloid leukemia. Klin. onkogematol. 2010; 3(1): 47–52. (In Russ.)].
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The problem of adherence to therapy in chronic myeloid leukemia: understanding the patient and making a decision

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF MYELOID MALIGNANCIES , ,

E.Yu. Chelysheva1, A.V. Galaktionova2, and A.G. Turkina1

1 Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

2 ANO “CO-operation project”, Moscow, Russian Federation

ABSTRACT

This article prepared by hematologists and the psychologist raises the problem of adherence to therapy in chronic myeloid leukemia. Poor adherence to therapy can worsen treatment outcomes. Patients who take less than 90 % of prescribed imatinib have lower chances to achieve clinically significant deep remission. It is shown that adherence rates decrease over time. Methods for measurement of adherence have limitations and do not always reflect an actual situation. It is noted that long-term treatment using medication in a form of tablets has its peculiarities associated with the necessity of a patient’s clear understanding of treatment goals, appropriate information on therapy aspects, and correction of side effects. The data on tyrosine kinase inhibitors regimens in chronic myeloid leukemia are included. The causes of poor adherence to therapy related to a particular mode of treatment and psychological status of the patient are described. Practical recommendations on adherence improvement are given.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, adherence to therapy

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REFERENCES

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Cardiovascular complications of chronic myeloid leukemia treated with tyrosine kinase inhibitors

COMPLICATIONS OF ANTITUMOR TREATMENT , , ,

G.E. Gendlin, L.M. Makeeva, E.I. Emelina, K.V. Shuikova, G.I. Storozhakov

 FGEI HPE RNRMU named after N.I. Pirogov of Russian MoH, Moscow, Russian Federation

ABSTRACT

The achieved nowadays success in oncohematology patients’ treatment is primarily associated with the development of targeted therapy, including invention of specific tyrosine kinase inhibitors for chronic myeloid leukemia treatment (imatinib, nilotinib and dasatinib,). However, along with the high efficacy, these medicines have certain toxicities. Cardiovascular complications of tyrosine kinase inhibitors therapy of chronic myeloid leukemia are described in this review article. Taking onto consideration the fact that therapy with these medicines can cause rear but serious side effects. It is necessary to consider the probability of cardiotoxicity, arterial occlusion of various diameter and pulmonary hypertension development before prescription. In order to minimize side effects patients examination is recommended before treatment initiation for recognition of initial cardiovascular diseases, as well as thorough control of cardiovascular condition throughout the treatment.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, cardiac toxicity, targeted therapy

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