clinical practice

Use of Blinatumomab in Acute Lymphoblastic Leukemia in Municipal Healthcare: A Case Report

AUTOIMMUNE THROMBOCYTOPENIA , ,

VA Shuvaev1,2, OV Ushakova1, EI Mullo1, TV Tolstykh1, NZ Triputen1

1 VV Veresaev Municipal Clinical Hospital, 10 Lobnenskaya str., Moscow, Russian Federation, 127644

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

For correspondence: Vasilii Anatolevich Shuvaev, MD, PhD, 10 Lobnenskaya str., Moscow, Russian Federation, 127644; e-mail: shuvaev77@mail.ru

For citation: Shuvaev VA, Ushakova OV, Mullo EI, et al. Use of Blinatumomab in Acute Lymphoblastic Leukemia in Municipal Healthcare: A Case Report. Clinical oncohematology. 2021;14(2):198–203. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-198-203

ABSTRACT

Acute lymphoblastic leukemia is one of the groups of most challenging malignant neoplasms of hematopoietic tissue. Despite the success in achieving remission induction in primary patients, later, most of them develop disease relapses. Overall and disease-free survivals have to be improved, which cannot be achieved solely with chemotherapy intensification. The new target drugs and cell technologies improve the treatment options for the resistant forms and relapses of acute lymphoblastic leukemia. The effective use of new drugs presupposes their timely assignment which can be ensured by their availability in routine clinical practice. The provided case report describes the successful use of bispecific antibody blinatumomab for treating an early relapse of acute lymphoblastic leukemia in the clinical practice within the municipal healthcare system.

Keywords: acute lymphoblastic leukemia, clinical practice, target therapy, blinatumomab.

Received: September 22, 2020

Accepted: February 3, 2021

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Статистика Plumx английский

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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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Targeted Therapy of Myelofibrosis

MYELOID TUMORS , , , , ,

OYu Vinogradova1,3,4, VA Shuvaev2, IS Martynkevich2, MM Pankrashkina1,3, MS Fominykh2, EV Efremova2, KYu Krutikova2, LB Polushkina2, NN Sharkunov1, SV Voloshin2, AV Chechetkin2

1SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

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

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

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

For correspondence: Ol’ga Yur’evna Vinogradova, MD, PhD, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284; Tel.: 8(495)945-97-61; e-mail: olgavinz@mail.ru.

For citation: Vinogradova OYu, Shuvaev VA, Martynkevich IS, et al. Targeted Therapy of Myelofibrosis. Clinical oncohematology. 2017;10(4):471–8 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-471-478

ABSTRACT

Background. Myelofibrosis (primary myelofibrosis, post-essential trombocythemia myelofibrosis, post-polycythemia myelofibrosis) is the most complex and pressing problem among all Ph-negative myeloproliferative diseases. The present article summarizes the author’s experience of using new Janus kinase inhibitors in routine clinical practice, and compares the data with the results of other clinical research.

Aim. To evaluate the use of ruxolitinib in patients with myelofibrosis.

Materials & Methods. Our analysis includes 48 patients (21 men and 27 women) with histologically verified myelofibrosis (primary myelofibrosis in 36 cases, post-essential trombocythemia myelofibrosis in 10 cases, and post-polycythemia myelofibrosis in 2 cases) in a chronic stage. All patients received ruxolitinib. Median age at the start of therapy was 60 years (range from 35 to 79). Massive splenomegaly (≥ 10 cm below the costal margin) was found in 34 (71 %) of 48 patients. The initial dose of ruxolitinib was determined by the platelet level. The efficacy of the therapy was evaluated in accordance with ELN 2013 criteria.

Results. Median duration of treatment was 18 months (range from 1 to 50 months). Symptoms of intoxication were relieved in 33 of 37 patients (89 %). The spleen size decreased in 64 % of patients. In 33 % of cases spleen size did not change, whereas an increase was observed in 3 % of patients. In the majority of patients hemoglobin level remained stable through the course of treatment. Three of 14 transfusion dependent patients did not require blood transfusions after 3 months of therapy. In patients with high thrombocyte levels prior to ruxolitinib therapy the mean level was approaching normal by the end of the 1st month of treatment. The median JAK2V617F mutant allele burden at the beginning treatment was 56.5 % (n = 20; 22.5–126.1 %). After 6 moths of treatment it accounted for 62.3 % (n = 11; 25.4–79.7 %) and in 12 months accounted for 47.4 % (n = 12; 14.2–102.2 %). By the time of the analysis 42 of 48 patients continued the ruxolitinib treatment (88 %). Death occurred in 4 patients. Overall 1-year (92 %) and 2-year (87 %) survival corresponds to the data of COMFORT-I, COMFORT-II and JUMP clinical trials.

Conclusion. Ruxolitinib showed to be an effective treatment for myelofibrosis. The most pronounced and rapid effect ruxolitinib had on the spleen size and the symptoms of intoxication. The tolerability of ruxolitinib was satisfactory in the majority of patients. According to the author’s data, ruxolitinib had a small impact on the JAK2V617F mutant allele burden. The overall survival rate in patients with myelofibrosis, receiving ruxolitinib in the clinical setting was similar to that of in the clinical trials.

Keywords: primary myelofibrosis, post-essential trombocythemia myelofibrosis, post-polycythemia myelofibrosis, JAK2V617F, ruxolitinib, clinical practice, targeted therapy.

Received: February 11, 2017

Accepted: May 22, 2017

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REFERENCES

  1. Абдулкадыров К.М., Шуваев В.А., Мартынкевич И.С. Миелопролиферативные новообразования. М.: Littera, 2016. 304 с.[Abdulkadyrov KM, Shuvayev VA, Martynkevich IS. Mieloproliferativnye novoobrazovaniya. (Myeloproliferative Neoplasms.) Moscow: Littera Publ.; 2016. 304 p. (In Russ)]
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  16. Al-Ali HK, Griesshammer M, le Coutre P, et al. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial. Haematologica. 2016;101(9):1065–73. doi: 10.3324/haematol.2016.143677.

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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Value of Patient-Reported Outcomes in Oncohematology

QUALITY OF LIFE , , ,

T.I. Ionova1, S. Salek2, Е. Оliva3

1 International Quality of Life Research Center, 1 office 152, Artilleriiskaya str., Saint Petersburg, Russian Federation, 191014

2 Cardiff University, Pharmacoeconomics Department, Redwood Building King Edward VII Avenue Cardiff, CF10 3NB, UK

3 Hematology Division, Azienda Ospedaliera B-M-M, Via Melacrino, 89100 Regio Calabria, Italy

For correspondence: T.I. Ionova, DSci, Professor, 1 office 152, Artilleriiskaya str., Saint Petersburg, Russian Federation, 191014; Tel: +7(812)579-61-38; e-mail: tation16@gmail.com

For citation: Ionova T.I., Salek S., Oliva E. Value of Patient-Reported Outcomes in Oncohematology. Klin. Onkogematol. 2014; 7(4): 573–576 (In Russ.).

ABSTRACT

One of priorities of modern medical science is the patient-oriented care. This approach presupposes that patient management should be based not only on analysis of clinical and lab test findings but also on reports made by the patient himself. These reports permit to perform a thorough analysis of patient’s problems and to obtain more data on the treatment effectiveness. Quality of life (QoL) and symptoms are key factors in patient-reported outcomes (PRO). The past decade has been characterized by increased attention paid by the medical community to patient’s own sensations throughout the treatment. The importance of this principle is confirmed by the fact that “Quality of Life in Hematology” was declared as the 2012–2013 theme of the year by the European Hematology Association. Partient-reported outcomes permit to obtain information that cannot be obtained from other sources. It is especially important when new treatment methods are selected and when new approaches to palliative care are developed.

Keywords: patient-reported outcomes, quality of life, symptoms, clinical practice.

Accepted: September 15, 2014

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