pharmacoeconomics

Pharmacoeconomic Analysis of Gilteritinib in the Therapy of Adult Patients with Relapsed/Refractory Acute Myeloid Leukemias with FLT3 Mutation

AUTOIMMUNE THROMBOCYTOPENIA ,

AS Kolbin1,2, YuM Gomon1, YuE Balykina2, MA Proskurin2

1 IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

2 Saint Petersburg State University, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

For correspondence: Yuliya Mikhailovna Gomon, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(911)960-62-68; e-mail: gomonmd@yandex.ru

For citation: Kolbin AS, Gomon YuM, Balykina YuE, Proskurin MA. Pharmacoeconomic Analysis of Gilteritinib in the Therapy of Adult Patients with Relapsed/Refractory Acute Myeloid Leukemias with FLT3 Mutation. Clinical oncohematology. 2022;15(1):85–96. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-85-96

ABSTRACT

Background. The implementation of new FLT3-targeted drugs in clinical practice has changed the approaches to the management of patients with acute myeloid leukemias (AML) with FLT3 mutation. One of these drugs is gilteritinib, approved by FDA in 2018 as a drug of choice in the therapy of adult patients with relapsed/refractory AML with FLT3 mutation.

Aim. To assess the economic feasibility of gilteritinib in the therapy of adult patients with relapsed/refractory AML with FLT3 mutation.

Materials & Methods. Pharmacoeconomic modelling was based on Markov and decision-tree models. Incremental cost-effectiveness ratio (ICER) was calculated relative to the efficiency indicator “overall survival”. Its values were compared with those calculated for venetoclax as reference drug, which has been already included in Essential Drug List and used as a first-line drug in this population if high-dose chemotherapy therapy is contraindicated. A Budget Impact Analysis has been made.

Results. Gilteritinib proved to be not only more effective in terms of overall survival (median 9.3 vs. 5.6 months), but also more cost-intensive (7,408,108 vs. 1,685,356 rubles a year) compared to the currently used polychemotherapy regimens. However, the difference of ICER with venetoclax was +4,89 % of total costs. The Budget Impact Analysis showed that the total economic load of implementing gilteritinib in clinical practice throughout 3 years will be 8,628,658,505 rubles.

Conclusion. Gilteritinib therapy is economically feasible and viable for adult patients with relapsed/refractory AML with FLT3 mutation.

Keywords: gilteritinib, FLT3 mutation, acute myeloid leukemias, pharmacoeconomics, incremental cost-effectiveness ratio.

Received: July 8, 2021

Accepted: November 21, 2021

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Статистика Plumx английский

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Hodgkin’s Lymphoma: Analysis Results of Volgograd Regional Registry

LYMPHOID TUMORS , , , , , ,

KD Kaplanov1,2, NP Volkov1, TYu Klitochenko1, IV Matveeva1, AL Shipaeva1, MN Shirokova1, NV Davydova3, EG Gemdzhian4

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

2 Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081

3 Consultation and Diagnosis Polyclinic No. 2, 114A Angarskaya str., Volgograd, Russian Federation, 400081

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

For correspondence: Kamil Daniyalovich Kaplanov, MD, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Hodgkin’s Lymphoma: Analysis Results of Volgograd Regional Registry. Clinical oncohematology. 2019;12(4):363–76 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-363-376

ABSTRACT

Background. The present paper discusses feasibility of first- and second-line therapies as well as the significance of different risk factors in the population of all patients with newly diagnosed Hodgkin’s lymphomas (HL) in a 14-year period based on the data of Volgograd regional registry.

Materials & Methods. During the period 2003 to 2017 the population registry of Department of Hematology of Volgograd Regional Clinical Oncology Dispensary included the data of all the patients with newly diagnosed HL (n = 622): 272 (44 %) men and 350 (56 %) women aged 18 to 84 years (mean age 38 years, median age 33 years). There were 97 (16 %) patients with early stages and without risk factors, 165 (27 %) patients with early stages and risk factors, 360 (59 %) patients with advanced stages, 308 (50 %) patients with toxic symptoms (stage B), and 179 (29 %) patients with bulky tumor lesions (≥ 10 cm). ABVD treatment regimen was administered in 190 (30.5 %) patients, increased-dose BEACO(D)PP in 39 (6 %) patients, BEACO(D)PP-14 in 159 (26 %) patients, standard BEACO(D)PP in 200 (32 %) patients, IVDG in 25 (4 %) patients, and other regimens in 9 (1.5 %) patients. The second-line treatment was administered in 120 (19 %) out of 622 patients. By the end of August 2018, the number of followed-up patients was 514 (83 %), 108 (17 %) patients had died. The prognostic value of the International Prognostic Score (IPS), PET, and other factors was assessed by means of Cox’s multivariate regression analysis. Pharmacoeconomic analysis of differences between options of first-line therapy was based on Markov model.

Results. In the group of patients with advanced HL stages treated with escalated BEACO(D)PP (the increased-dose regimen and BEACO(D)PP-14) 5- and 10-year overall survival (OS) was 83 % and 74 %, respectively, OS median was not reached. On standard BEACO(D)PP patients with advanced HL stages had OS median of 139 months (11.6 years) and 5- and 10-year OS of 68 % and 54 %, respectively (p = 0,012). In the group of patients with early stages and poor prognosis treated with escalated regimens BEACO(D)PP 5- and 10- year OS was 100 % and 90 %, respectively, in the combined group treated with ABVD and standard BEACO(D)PP it was 83 % and 75 % (p = 0.035). Replacement of procarbazine with dacarbazine in the standard and increased-dose BEACOPP regimens did not affect treatment efficacy. Markov analysis demonstrated the advantages of the escalated regimens for treatment of early stages with poor prognosis and advanced stages in terms of life years gained. Out of 7 IPS factors male sex, age ≥ 45 years, hemoglobin < 105 g/L, and albumin < 40 mg/L significantly impacted OS. Based on these data an adjusted prognostic index was suggested.

Conclusion. The advantage of the escalated strategy of first-line therapy in HL is reflected in survival parameters and is based on pharmacoeconomic evidence. The significance of some laboratory IPS risk factors can be reviewed; most obvious is increasing importance of PET for predicting the need for salvage therapy.

Keywords: Hodgkin’s lymphoma, BEACO(D)PP, ABVD, International Prognostic Score, survival analysis, pharmacoeconomics, Markov model, life years gained (LYG), incremental cost-effectiveness ratio (ICER).

Received: February 21, 2019

Accepted: September 17, 2019

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Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues

LYMPHOID TUMORS , , , , , ,

KD Kaplanov1,2, NP Volkov1, TYu Klitochenko1, IV Matveeva1, AL Shipaeva1, MN Shirokova1, NV Davydova3, EG Gemdzhian4, DS Abramov5, DM Konovalov5, GL Snigur2, NA Red’kina1

1 Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

2 Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081

3 Consultation and Diagnosis Polyclinic No. 2, 114A Angarskaya str., Volgograd, Russian Federation, 400081

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

5 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117997

For correspondence: Kamil’ Daniyalovich Kaplanov, MD, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues. Clinical oncohematology. 2019;12(2):154–64.

DOI: 10.21320/2500-2139-2019-12-2-154-164

ABSTRACT

Background & Aims. At least one third of patients with diffuse large B-cell lymphoma (DLBCL) are resistant to first-line therapy. R-CHOP chemo-immunotherapy does not yield acceptable results in high-risk patients. Effectiveness of options based either on increasing the dose intensity or on including auto-HSCT into the first-line therapy was not supported by the results of controlled studies. With this background the present study focuses on options, issues and failures of first-line on the basis of long-term follow-up of DLBCL patient population in the Volgograd Region.

Materials & Methods. From 2004 to 2017 the population-based registry of the Hematology Department in the Volgograd Regional Clinical Oncology Dispensary included all 492 primary DLBCL patients: 235 (48 %) men and 257 (52 %) women aged 18 to 88 years. Mean and median age was 59 and 61 years, respectively. CHOP therapy was administered to 206 (42 %) patients, and 223 (45 %) patients received R-CHOP. Other regimens including NHL-BFM-90 and R-DA-EPOCH were used only in 63 (13 %) patients. Second- and third-line therapies were administered to 145 (30 %) and 54 (11 %) patients, respectively. Value of the International Prognostic Index (IPI) and immunomorphologic characteristics was determined by multivariate Cox regression analysis. Pharmacoeconomic aspect of first-line therapy failures was analyzed using Markov model.

Results. Improvement of DLBCL therapy effects with the use of R-CHOP chemo-immunotherapy is particularly obvious in the groups with favorable and intermediate prognosis with 5-year overall survival (OS) of 90 % and 69 %, respectively. R-CHOP results are not considered to be satisfactory in the high-risk group: 5-year OS was 38 %. Pharmacoeconomic analysis proves the advantage of chemo-immunotherapy strategy in comparison with the period before rituximab era in terms of the life years gained (LYG) and the incremental cost-effectiveness ratio (ICER). With respect to immunotherapy effects the most significant immunomorphologic parameter is bcl-2 tumor cell expression. In the group of patients with bcl-2 > 50 % 5-year OS was 61 % with median of 88 months, event-free survival (EFS) was 52 % with median of 62 months. In the group without bcl-2 expression above the threshold 5-year OS and EFS were 88 % and 75 %, respectively, medians were not achieved. With c-myc and bcl-2 coexpression EFS and OS appeared to be even worse: 5-year EFS was 29 % with median of 6 months, and 5-year OS was 31 % with median of 15 months.

Conclusion. The analysis of actual practice demonstrates the need for new options of first-line therapy for DLBCL high-risk patients and also for introducing new discriminating prognostic factors which include the IPI-independent ones.

Keywords: diffuse large B-cell lymphoma, R-CHOP, chemoimmunotherapy, survival, pharmacoeconomics, Markov model, life years gained (LYG), incremental cost-effectiveness ratio (ICER).

Received: July 16, 2018

Accepted: January 10, 2019

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First-Line Treatment of Mantle-Cell Lymphoma: Analysis of Effectiveness and Cost-Effectiveness

LYMPHOID TUMORS , , , ,

KD Kaplanov1, NP Volkov1, TYu Klitochenko1, AL Shipaeva1, IV Matveeva1, MN Shirokova1, AC Proskurina1, NA Red’kina1, EG Gemdzhyan2

1 Volgograd Regional Clinical Oncologic Centre, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

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

For correspondence: Kamil’ Daniyalovich Kaplanov, MD, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Volkov NP, Klitochenko TYu, et al. First-Line Treatment of Mantle-Cell Lymphoma: Analysis of Effectiveness and Cost-Effectiveness. Clinical oncohematology. 2018;11(2):150–9.

DOI: 10.21320/2500-2139-2018-11-2-150-159

ABSTRACT

Aim. To study the correlation between efficacy of mantle-cell lymphoma treatment in clinical practice and failure of first-line therapy and direct expenses depending on the first-line therapy selection.

Methods. During the period from 2008 to 2016 a comparative single-center controlled trial was performed to evaluate the effectiveness and toxicity of R-hyper-CVAD-R-HD-AraC (n = 16) regimen. The control group included patients treated with 6–8 cycles of R-CHOP (n = 39). Cytarabine dose was lower than the original regimen and contained not more than 1 g/m2 twice a day for 2 days. R-hyper-CVAD regimen included the standard drug doses. R-HD-AraC treatment started on day 28 from the beginning of the R-hyper-CVAD therapy. The R-hyper-CVAD-R-HD-AraC group consisted of patients with the following characteristics: the median age was 56 years (range 40–66), older than 60 — 6 (38 %), male patients — 12 (75 %), stage IV — 12 (75 %), bulky — 7 (44 %), with bone marrow involved — 11 (69 %), MIPIb high-risk — 8 (50 %), blastoid variant — 7 (44 %). Only 2 patients of the R-hyper-CVAD-R-HD-AraC group received high-dose consolidation treatment with autologous HSC transplantation. HSCT was not performed in the control group. The results of comparative analysis were adjusted to age. In terms of the other significant factors the groups under comparison were similar.

Results. All the patients of the study group were treated with 3 R-hyper-CVAD and 3 R-HD-AraC regimens. The rate of complete remission was significantly higher than in the control group —12 (75 %) vs. 14 (36 %). No differences were observed in the 5-year overall survival: 55 % in the R-hyper-CVAD-R-HD-AraC group and 58 % in the R-CHOP group (p = 0.75). Second-line therapy was received by 8 out of 15 (47 %) patients treated with R-hyper-CVAD-R-HD-AraC, and by 18 out of 23 (78 %) patients treated with R-CHOP. Median time before second-line therapy was significantly higher in the R-hyper-CVAD-R-HD-AraC group — 26 vs. 6 months (p = 0.018). The costs of the first and subsequent therapy lines were analysed using a Markov model. Cost analysis of first-line therapy variants to be compared was based on cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER). The analysis proved the cost-effectiveness of R-hyper-CVAD-R-HD-AraC program.

Conclusion. R-hyper-CVAD-R-HD-AraC program meets eligibility criteria for effectiveness, toxicity and cost-effectiveness and can, therefore, be recommended as first-line therapy of mantle-cell lymphoma and be used for the further comparative clinical trials.

Keywords: mantle-cell lymphoma, immunochemotherapy, pharmacoeconomics, Markov model, cost-effectiveness analysis.

Received: January 7, 2018

Accepted: March 3, 2018

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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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