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

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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Acute myeloid leukemias with t(7;21)(p22;q22) translocation, 5q- deletion, CD56 expression, and hemophagocytosis: case report and literature review

N.N. Mamayev1, T.L. Gindina1, E.G. Boychenko2, A.V. Gorbunova1, V.M. Kravtsova1, N.V. Stancheva1, P.V. Kozhokar1, O.V. Paina1, L.S. Zubarovskaya1, and B.V. Afanasyev1

1 R.M. Gorbacheva Institute of Pediatric Oncology, Hematology and Transplantology, I.P. Pavlov Saint Petersburg State Medical University, Saint Petersburg, Russian Federation

2 Children’s City Hospital #1, Saint Petersburg, Russian Federation


ABSTRACT

We present the clinical and laboratory data on a 13-year old patient with the recently described variant of CD56-positive acute myeloid leukemia with criptic t(7;21)(p22;q22) translocation involving rearrangements of RUNX1 and USP42 genes, 5q deletion, and hemophagocytosis. According to the literature, this rare recently described AML subvariant mostly occurs in males, is resistant to chemotherapy, and can be successfully treated using allogeneic hematopoietic stem cell transplantation.


Keywords: acute myeloid leukemia, t(7;21)(p22;q22), 5q-, CD56+, resistance to chemotherapy, erythrophagocytosis, alloHSCT.

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REFERENCES

  1. Paulsson K., Bekassy A.N., Olofsson T. et al. A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquting-specific protease gene USP42. Leukemia 2006; 20(2): 224–9.
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  5. Jeandidier E., Gervais C., Radford-Weiss I. et al. A cytogenetic study of 397 consecutive acute myeloid leukemia cases identified three with a t(7;21) associated with 5q abnormalities and exhibiting similar clinical and biological features, suggesting a new, rare acute myeloid leukemia entity. Cancer Genet. 2012; 205(7–8): 365–72.
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Genfatinib® therapy for chronic-phase chronic myeloid leukemia in routine clinical practice

T.V. Chagorova1, V.V. Yablokova2, P.A. Borkina3, and N.A. Pryanikova3

1 Regional Oncology Clinic, Penza, Russian Federation

2 Yaroslavl Regional Clinical Hospital, Yaroslavl, Russian Federation

3 Moscow Representative Office of GENFA LTD (United Kingdom), Moscow, Russian Federation


ABSTRACT

The article describes the outcomes of Genfatinib® therapy in routine clinical practice at the Regional Oncology Clinic (Penza) and Yaroslavl Regional Clinical Hospital (Yaroslavl). 62 patients with chronic myeloid leukemia (chronic phase) were treated at the above institutions from April 2012 to April 2013. The patients were assigned into the following groups: the first treatment group, where Genfatinib® was prescribed as an initial therapy at the time of diagnosis of chronic-phase chronic myeloid leukemia; the second group, where Genfatinib® was prescribed after the initial therapy with Gleevek®. The main objectives were assessment of the Genfatinib® efficacy (rates of complete or partial clinico-hematological, cytogenetic, and molecular responses), toxicity, and safety. It was shown that Genfatinib® used after previous therapy with Gleevek® caused no negative influence of the rates of clinico-hematological, cytogenetic, and molecular responses. In the patients who received Genfatinib® as an initial therapy, the complete clinico-hematological and cytogenetic and molecular responses were achieved by 3–5 and 3–6 months of treatment, respectively. The spectrum of adverse events observed with Genfatinib® therapy was similar to the one of Gleevek®.


Keywords: chronic myeloid leukemia, chronic phase, Genfatinib®, efficacy, safety.

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Refernces

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Clinico-hematological and molecular genetic variability of acute myeloid leukemia with CD7 expression on blasts cells

S.V. Gritsayev1, Z.V. Chubukina1, I.S. Martynkevich1, I.I. Kostroma1, T.V. Glazanova1, Ye.V. Petrova1, L.S. Martynenko1, S.A. Tiranova1, N.A. Potikhonova1, I.S. Zyuzgin2, L.N. Bubnova1, and K.M. Abdulkadyrov1

1 Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

2 Leningrad Regional Hospital, Saint Petersburg, Russian Federation


ABSTRACT

The objective of the study was to evaluate the heterogeneity of patients with acute myeloid leukemia with CD7 aberrant expression. The retrospective analysis of 31 AML patients’ laboratory and clinical data was performed. Marked morphological, cytogenetic, and molecular heterogeneity of AML with CD7 coexpression was established. Also, it was found that these patients could be stratified into groups by overall survival. Four patients with t(8;21) or t(15;17) translocations or inv(16) inversion were followed-up for 53, 33, 11, and 10 months, respectively. The median of OS was not reached among the patients with t(8;21), t(15;15), and inv(16). The median OS among 10 patients with normal karyotype with no FLT3-ITD mutation was 17 months. The median OS among 17 patients with other genetic abnormalities including 7 patients with normal karyotype and FLT3-ITD mutation was 8 months; p = 0.033. We conclude that CD7 expression on AML blast cells is not an independent prognostic factor.


Keywords: acute myeloid leukemia, myeloblasts, CD7 coexpression, karyotype, FLT3-ITD mutation.

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Quality of life and symptom profile in patients with chronic myeloid leukemia receiving dasatinib as а second-line therapy due to intolerance or resistance to imatinib

Ionova1,2, D. Fedorenko1,2, T. Nikitina1, and K. Kurbatova1

1 N.I. Pirogov National Medico-surgical Center, Moscow, Russian Federation

2 International Center for Quality of Life Studies, Saint-Petersburg, Russian Federation


ABSTRACT

The article is focused on preliminary results of the observational study “Quality of life and symptom profile in imatinib-resistant or intolerant patients with chronic myeloid leukemia during disease-modifying treatment” (2011–2012). 56 imatinib-resistant or intolerant patients with chronic myeloid leukemia in chronic phase were included in the preliminary analysis. It was shown that prior to treatment with dasatinib more than one third of patients had severe or critical quality of life deterioration. Patients treated with standard doses of imatinib during the first-line treatment reported better quality of life than patients treated with high doses of imatinib. After 12 months of treatment with dasatinib, the majority of patients showed complete or partial cytogenetic response (62 %); most of the patients with complete cytogenetic response were treated with standard doses of imatinib during the first-line treatment (19 % vs 8 %). During treatment with dasatinib, stabilization of quality of life parameters was recorded with a slight trend towards improved vitality, mental health, and pain scales. In the majority of patients (68 %), the treatment response as improved or stabilized quality of life was observed. During treatment with dasatinib, severity of the most frequent disease- or treatment-specific symptoms decreased. In this observational study, it was shown that dasatinib therapy in the real-world practice is effective both in terms of clinical parameters and patient-reported outcomes, and characterized by good tolerability.


Keywords: quality of life, symptom profile, chronic myeloid leukemia, dasatinib.

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REFERENCES

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The problem of adherence to therapy in chronic myeloid leukemia: understanding the patient and making a decision

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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Cytogenetic remission as an important criterion for treatment efficacy in pediatric acute myeloid leukemia

E.W. Fleischman1, O.I. Sokova1, A.V. Popa2, V.S. Nemirovchenko2, L.N. Konstantinova1, and N.F. Metelkova1

1 Institute of Сarcinogenesis, N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

2 Pediatric Oncology and Hematology Institute, N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation


ABSTRACT

The results of repeated karyotype analyses in the disease course in 43 children with de novo acute myeloid leukemia (AML) are presented. Patients with clonal bone marrow chromosome abnormalities at diagnosis were included. The follow-up period lasted from 4 to 79 months (median 23 months). The patient cohort was divided into two groups: the standard-risk group and high-risk group. The first group included 13 children with t(8;21)(q22;q22), inv(16)(p13;q22), and t(16;16)(p13;q22). The rest of the patients (30 cases) formed the second group. After assessment of results of bone marrow chromosome analysis at 1–3 months of the treatment, the conclusion was drawn that persistence even single cytogenetically abnormal cell at the start of morphological remission is an unfavorable prognostic sign. It is illustrated by comparison of relapse-free survival (RFS) in two groups of patients: with cytogenetic remission at the onset of morphologic remission (group 1) or with no remission (group 2). RFS was 64.1 ± 10.3 % in the first group. In the second group, one patient is at 20th month of the first CCR and four remaining patients relapsed at 3–20th months (p = 0.018). Another conclusion can be made from our data. Persistence in bone marrow cytogenetically abnormal cells at the beginning of morphological remission can be observed in patients with favorable chromosome markers and patients from other prognostic groups. This finding was prognostically unfavorable regardless of risk-group. Thus, persistence of cytogenetically abnormal cells in bone marrow at the time of morphological remission achieved is a more sensitive criterion for poor outcome than the baseline karyotype (risk groups). The facts obtained show an importance of cytogenetic analysis performance not only at diagnosis but also at the onset of morphologic remission.


Keywords: pediatric acute myeloid leukemia, chromosome markers, cytogenetic remission.

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