AUTOIMMUNE THROMBOCYTOPENIA

Efficacy and Safety of Midostaurin Combined with Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation

AUTOIMMUNE THROMBOCYTOPENIA ,

SN Bondarenko1, AG Smirnova1, BI Ayubova1, EV Karyagina2, OS Uspenskaya3, YuS Neredko4, AP Kochergina5, IA Samorodova6, EA Pashneva7, YuS Chernykh8, YuA Dunaev9, NB Esef’eva10, RK Il’yasov11, TI Brazhkina12, IA Novokreshchenova13, ZK Simavonyan14, EI Kuzub15, VI Bakhtina16, TI Olkhovich17, MV Burundukova18, EV Babenko1, YuD Oleinikova1, IM Barkhatov1, TL Gindina1, IS Moiseev1, AD Kulagin1

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

2 Municipal Hospital No. 15, 4 Avangardnaya ul., Saint Petersburg, Russian Federation, 198205

3 Leningrad Regional Clinical Hospital, 45 korp. 2A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

4 Stavropol Krai Clinical Oncology Dispensary, 182a Oktyabrskaya ul., Stavropol, Russian Federation, 355047

5 Krai Clinical Hospital, 1 Lyapidevskogo ul., Barnaul, Russian Federation, 656024

6 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

7 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki ul., Volgograd, Russian Federation, 400138

8 MF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina ul., Moscow, Russian Federation, 129110

9 Arkhangelsk Regional Clinical Hospital, 292 Lomonosova pr-t, Arkhangelsk, Russian Federation, 163045

10 Ulyanovsk Regional Clinical Hospital, 7 III Internatsionala ul., Ulyanovsk, Russian Federation, 432017

11 VM Efetov Crimea Republican Clinical Oncology Dispensary, 49A Bespalova ul., Simferopol, Russian Federation, 295007

12 Ivanovo Regional Clinical Hospital, 1 Lyubimova ul., Ivanovo, Russian Federation, 153040

13 RZhD-Meditsina Clinical Hospital, 15 1-i Krasnoflotskii per., Smolensk, Russian Federation, 214025

14 AI Burnazyan Federal Medical Biophysical Center, 23 Marshala Novikova ul., Moscow, Russian Federation, 123098

15 Rostov State Medical University Hospital, 29 Nakhichevanskii per., Rostov-on-Don, Russian Federation, 344022

16 Krasnoyarsk Krai Clinical Hospital, 3A Partizana Zheleznyaka ul., Krasnoyarsk, Russian Federation, 660022

17 Krasnoyarsk Interdistrict Clinical Hospital No. 7, 4 Akademika Pavlova ul., Krasnoyarsk, Russian Federation, 660003

18 Municipal Clinical Hospital No. 2, 21 Polzunova ul., Novosibirsk, Russian Federation, 630051

For correspondence: Sergei Nikolaevich Bondarenko, MD, PhD, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022; Tel.: +7(921)994-35-70; e-mail: dr.sergeybondarenko@gmail.com

For citation: Bondarenko SN, Smirnova AG, Ayubova BI, et al. Efficacy and Safety of Midostaurin Combined with Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation. Clinical oncohematology. 2022;15(2):167–75. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-167-175

ABSTRACT

Background. The detection of FLT3-ITD mutation in acute myeloid leukemia (AML) patients is associated with poor prognosis and is an indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first remission. Midostaurin is the first FLT3 inhibitor approved for the treatment of AML patients with FLT3 mutation in the Russian Federation in November 2019. This study deals with the initial experiences of using midostaurin in several centers for hematology in the Russian Federation.

Aim. To analyze the initial experiences of using midostaurin at different AML stages.

Materials & Methods. The study enrolled 42 patients with newly diagnosed AML with FLT3 mutation, who were treated with midostaurin combined with chemotherapy. Allo-HSCT was performed in 11 patients.

Results. The 2-year overall survival (OS) was 51 %, and the 2-year event-free survival (EFS) was 45 %. After achieving remission, the 2-year disease-free survival (DFS) was 58 %. The 1-year DFS of allo-HSCT recipients was 86 % (95% confidence interval [95% CI] 60–100 %) vs. 66 % in patients treated with chemotherapy without allo-HSCT (95% CI 34–98 %), respectively (p = 0.5). Hyperleukocytosis at disease onset was associated with high relapse risk. Midostaurin had to be discontinued in 5 % of cases due to atrial fibrillation and QTc prolongation.

Conclusion. The present study demonstrates the safety and importance of including midostaurin in the regimens for treating AML with FLT3 mutation. Midostaurin assignment for maintenance therapy, after allo-HSCT as well as without performing it, can result in considerable improvement of OS and DFS.

Keywords: acute myeloid leukemias, FLT3 mutations, targeted therapy, midostaurin.

Received: December 27, 2021

Accepted: March 20, 2022

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Evaluation of Heterozygosity Loss in STR-Loci of Tumor DNA in Multiple Myeloma Patients with Plasmacytoma Based on the Molecular Analysis of Complex Archival Tumor Samples

AUTOIMMUNE THROMBOCYTOPENIA ,

EE Nikulina1, MV Firsova1, NV Risinskaya1, YaA Kozhevnikova2, MV Solov’ev1, TV Abramova1, TN Obukhova1, AM Kovrigina1, AB Sudarikov1, LP Mendeleeva1

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

2 Faculty of Fundamental Medicine, MV Lomonosov Moscow State University, 27-1 Lomonosovskii pr-t, Moscow, Russian Federation, 119192

For correspondence: Elena Evgen’evna Nikulina, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: lenysh2007@rambler.ru

For citation: Nikulina EE, Firsova MV, Risinskaya NV, et al. Evaluation of Heterozygosity Loss in STR-Loci of Tumor DNA in Multiple Myeloma Patients with Plasmacytoma Based on the Molecular Analysis of Complex Archival Tumor Samples. Clinical oncohematology. 2022;15(2):156–66. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-156-166

ABSTRACT

Background. Multiple myeloma (MM) is a hematological malignancy with plasma cells as substrate. Sometimes MM is characterized by plasmacytomas, i.e., intra- and extraosseous tumors. A paraffin block containing plasmacytoma substrate provides valuable material to be used for analyzing the molecular biological characteristics of tumor. STR-profiling is a method for simultaneous evaluation of DNA degradation and integral assessment of tumor genome stability.

Aim. To describe STR-profiles of plasmacytoma DNA isolated from archival samples and to assess the integral stability of tumor genome against control DNA of patients.

Materials & Methods. The retrospective study enrolled 10 MM patients with plasmacytoma (7 women and 3 men) aged 34–62 years (median 53.5 years) who were treated at the National Research Center for Hematology from 2013 to 2021. Paired tumor/control DNA samples were obtained from all 10 patients.

Results. The present paper takes the first step in attempting a large-scale molecular genetic study of MM and provides first findings on the loss of heterozygosity (LOH) in plasmacytoma genome. All 10 patients showed LOH variants with different allelic loads having either deletion/quantitatively neutral LOH or duplication of one of the two alleles and involving 1–8 STR-loci. In plasmacytoma substrate the number of loci with LOH tended to be higher in the group with MM relapses compared with plasmacytomas identified at disease onset. According to the data analysis, LOH was frequently (in 4 out of 10 cases) detected on chromosomes 1 (1q42), 6 (6q14), 7 (7q21.11), 13 (13q31.1), and 21 (21q21.1).

Conclusion. The present paper shows the effectiveness of molecular analysis of DNAs being isolated from complex archival material consisting of paraffin blocks with plasmacytomas.

Keywords: multiple myeloma, plasmacytoma, loss of heterozygosity, STR-profiling.

Received: October 25, 2021

Accepted: January 28, 2022

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ROR-1 Expression in the Diagnosis and Monitoring of Minimal Residual Disease in Chronic Lymphocytic Leukemia

AUTOIMMUNE THROMBOCYTOPENIA

EV Pochtar1, SA Lugovskaya1, EV Naumova1, EA Dmitrieva2, VV Dolgov1

1 Russian Medical Academy of Postgraduate Education, 2/1 Barrikadnaya ul., Moscow, Russian Federation, 125993

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

For correspondence: Evgenii Vladimirovich Pochtar, 12 apt. 53 Verkhnyaya Maslovka, Moscow, Russian Federation, 127083; Tel.: +7(917)550-06-38; e-mail: pochtar_ev@mail.ru

For citation: Pochtar EV, Lugovskaya SA, Naumova EV, et al. ROR-1 Expression in the Diagnosis and Monitoring of Minimal Residual Disease in Chronic Lymphocytic Leukemia. Clinical oncohematology. 2022;15(2):148–55. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-148-155

ABSTRACT

Background. In view of similar morphological and phenotypic characteristics of some B-cell lymphoproliferative diseases and despite the known phenotype of tumor cells, a search is currently underway for new diagnostic markers, the expression of which remains stable during chronic lymphocytic leukemia (CLL) treatment and can be used for both diagnosis and assessment of residual tumor population. One of such markers is ROR-1.

Aim. To assess the expression and feasibility of the ROR-1 marker using В-lymphocytes in minimal residual disease (MRD) dynamics and monitoring in CLL.

Materials & Methods. Hematological and immunophenotypic analyses were performed in 110 CLL patients (50 of them with newly diagnosed disease and 60 on therapy). In addition to that, 20 patients with reactive lymphocytosis and 32 donors were examined. The ROR-1 expression in В-lymphocytes were measured with FACS Canto II flow cytometer using the following monoclonal antibody panel: CD45, CD19, CD20, and ROR-1.

Results. The analysis showed that ROR-1 is essentially not expressed in normal and reactive В-lymphocytes and is detected in 100 % of CLL tumor cells both at disease onset and on therapy. The ROR-1 expression does not change during CLL treatment and can be used not only for CLL diagnosis but also for detection of MRD. Bone marrow aspirates (n = 64) and peripheral blood samples (n = 6) were analysed for MRD assessment by two methods: according to the standardized protocol, recommended by ERIC (European Research Initiative on CLL) in 2007, with FACS Canto II flow cytometer (BD Biosciences) and using DuraClone RE CLB Tube (Beckman Coulter) with Navious flow cytometer (Beckman Coulter).

Conclusion. The comparison of the two methods for MRD assessment, i.e., the standardized (ERIC) one and DuraClone RE CLB (Beckman Coulter) including ROR-1, yielded a high correlation between them (r = 0.9936.)

Keywords: ROR-1, chronic lymphocytic leukemia, minimal residual disease.

Received: December 27, 2021

Accepted: March 18, 2022

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Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA ,

EV Vaneeva, VA Rosin, DA Dyakonov, SV Samarina, IV Paramonov

Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027

For correspondence: Elena Viktorovna Vaneeva, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; Tel.: +7(922)975-23-34; e-mail: vaneeva.elena.vic@mail.ru

For citation: Vaneeva EV, Rosin VA, Dyakonov DA, et al. Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2022;15(2):140–7. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-140-147

ABSTRACT

Aim. To assess the prognostic value of pAKT1 and рSyk expression in DLBCL.

Materials & Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cut-off of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher’s exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test).

Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index > 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49–10.9; p < 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54–7.30; p = 0.002).

Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.

Keywords: diffuse large B-cell lymphoma, pAKT1 and pSyk expression, overall survival, progression-free survival.

Received: November 17, 2021

Accepted: March 2, 2022

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Treatment of Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

AUTOIMMUNE THROMBOCYTOPENIA

AS Luchinin

Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027

For correspondence: Aleksander Sergeevich Luchinin, MD, PhD, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; Tel.: +7(919)506-87-86; e-mail: glivec@mail.ru

For citation: Luchinin AS. Treatment of Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis. Clinical oncohematology. 2022;15(2):130–9. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-130-139

ABSTRACT

Background. Up to now, R-CHOP-21 therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) has been a standard option in the treatment of newly diagnosed diffuse large B-cell lymphoma (DLBCL). About 40–50 % of patients, however, show refractoriness to this therapy or develop early relapses.

Results. The outcomes of 22 clinical trials enrolling 9879 DLBCL patients were analyzed. The efficacies of different R-CHOP-21 therapy regimens were compared, and the progression-free-survivals were estimated. The network meta-analysis showed that, in the total cohort, the most effective first-line regimens were VenR-CHOP (hazard ratio [HR] 0.61; 95% confidence interval [95% CI] 0.37–1.00) and Pola-R-CHP (HR = 0.73; 95% CI 0.47–1.12). For non-GCB (ABC) subtype patients less than 60 years of age, R-ACVBP (HR = 0.31; 95% CI 0.12–0.79) and IR-CHOP (HR = 0.56; 95% CI 0.36–0.86) regimens appeared to be more effective than R-CHOP-21.

Conclusion. Today, the newly diagnosed DLBCL can be treated not only with R-CHOP-21, but also with alternative and more effective regimens. Their assignment, however, needs to be strictly personalized. IR-CHOP and R-ACVBP therapies can be administered in patients with non-GCB (ABC) subtype of DLBCL, if they are under 60 years of age. The list of these regimens can be further extended to include novel drugs, such as polatuzumab vedotin (its efficacy was confirmed by a randomized clinical trial) and venetoclax (its efficacy was confirmed by a non-randomized clinical trial).

Keywords: diffuse large B-cell lymphoma, meta-analysis.

Received: November 24, 2021

Accepted: March 7, 2022

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Protocol ALL-IC BFM 2002: Outcomes of Pediatric Acute Lymphoblastic Leukemia Treatment under Multi-Center Clinical Trial

AUTOIMMUNE THROMBOCYTOPENIA ,

TT Valiev1, MA Shervashidze1, IV Osipova2, TI Burlutskaya3, NA Popova4, NS Osmulskaya5, GA Aleskerova6, SL Sabantsev7, ZS Gordeeva7, VYu Smirnov8, OA Poberezhnaya8, SN Yuldasheva9, IA Babich10, NA Batmanova1, SR Varfolomeeva1

1 Research Institute of Pediatric Oncology and Hematology, NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Pediatric Republican Clinical Hospital of Tatarstan, 140 Orenburgskii trakt, Kazan, Russian Federation, 420138

3 Pediatric Regional Clinical Hospital, 44 Gubkina ul., Belgorod, Russian Federation, 308036

4 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki ul., Volgograd, Russian Federation, 400138

5 Regional Pediatric Clinical Hospital, 77 Kuibysheva ul., Omsk, Russian Federation, 644001

6 Azerbaijan National Center for Oncology, 79b G. Zardabi ul., Baku, Azerbaijan, AZ1011

7 LI Sokolova Ioshkar-Ola Pediatric Municipal Hospital, 104 Volkova ul., Ioshkar-Ola, Russian Federation, 424004

8 Kaluga Regional Clinical Pediatric Hospital, 1 Vishnevskogo ul., Kaluga, Russian Federation, 248007

9 VK Gusak Institute of Emergency and Reconstructive surgery, 47 Leninskii pr-t, Donetsk, Donetsk People’s Republic, 83003

10 Regional Pediatric Hospital, 311 Lenina ul., Yuzhno-Sakhalinsk, Russian Federation, 693006

For correspondence: Prof. Timur Teimurazovich Valiev, MD, PhD, 23 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: timurvaliev@mail.ru

For citation: Valiev TT, Shervashidze MA, Osipova IV, et al. Protocol ALL-IC BFM 2002: Outcomes of Pediatric Acute Lymphoblastic Leukemia Treatment under Multi-Center Clinical Trial. Clinical oncohematology. 2022;15(2):119–29. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-119-129

ABSTRACT

Background. Programs of pediatric acute lymphoblastic leukemia (ALL) treatment, developed by the BFM (Berlin-Frankfurt-Munster) Group in 2002, remain one the most effective in the world. Long-term (10–15 years) overall survival in ALL children is above 90 %. Great progress in ALL treatment provided ground for including the ALL-IC BFM 2002 protocol into the Clinical Guidelines in 2020 (ID: 529).

Aim. To present the outcomes of ALL treatment in children according to ALL-IC BFM 2002 under the multi-center clinical trial.

Materials & Methods. From 01.11.2003 to 12.10.2021 the multi-center retrospective-prospective trial included 433 patients with newly diagnosed ALL, aged between 3 months and 21 years. The patients were aged from 0 to 12 (n = 344), from 12 to 18 (n = 70), and older than 12 years (n = 19). All of them were treated with ALL-IC BFM 2002. Overall (OS), disease-free (DFS), and event-free (EFS) survivals were estimated as of 01.12.2021.

Results. In the vast majority of patients (97.9 %, n = 424) complete clinical hematological remission was reached by Day 33 of the ALL-IC BFM 2002 treatment. The 10-year OS was 91.8 ± 1.5 %, DFS was 87.4 ± 1.8 %, and EFS was 84.1 ± 1.9 %. The 10-year OS in the groups of standard- and intermediate-risk patients was 92.8 ± 1.7 % and 94.6 ± 2.6 %, respectively, whereas in high-risk ALL relapse patients it was 71.1 ± 11.1 %.

Conclusion. The ALL-IC BFM 2002 protocol for treating pediatric ALL is reproducible in federal and regional clinics. The outcomes of the ALL-IC BFM 2002 treatment appeared to be impressive. They are comparable to those achieved in leading European and American clinics. To improve survival of high-risk patients, additional stratifying criteria are required, one of which should be the assessment of minimal residual disease (MRD). MRD detection became a basis for prognostic risk stratification under ALL-IC BFM 2009, the results of which will be presented in 2022–2023.

Keywords: acute lymphoblastic leukemia, treatment, ALL-IC BFM 2002, children.

Received: January 17, 2022

Accepted: March 25, 2022

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REFERENCES

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  10. Moricke A, Reiter A, Zimmermann M, et al. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. 2008;111(9):4477–89. doi: 10.1182/blood-2007-09-112920.
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From the editors

AUTOIMMUNE THROMBOCYTOPENIA

В журнале «Клиническая онкогематология. Фундаментальные исследования и клиническая практика» опубликована статья И.С. Моисеева и соавт. «Результаты российской многоцентровой кооперативной проспективно-ретроспективной наблюдательной программы лечения лимфомы Ходжкина RNWOHG-HD1» (2021;14(4):455–65). В разд. «Введение» в последнем абзаце (с. 458) напечатано: «К таким публикациям можно отнести ранний опыт применения полихимиотерапии СОРР/МОР с 25-летней ВБП около 50 % [20, 21], ABVD с 25-летней ВБП 73 % [21]…» Следует читать: «К таким публикациям можно отнести опыт применения самостоятельной лучевой терапии по радикальной программе с 25-летней ВБП 47 % и химиолучевой терапии с использованием схемы СОРР с 20-летней ВБП 81 % [20], а также применения химиотерапии по схеме МОРР или ABVD c 10-летней ВБП 62 и 75 % соответственно [21]…»

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Current Aspects in Early Diagnosis of Cardiotoxic Complications of Drug Therapy in Oncology: A Literature Review

AUTOIMMUNE THROMBOCYTOPENIA

GR Gimatdinova, OE Danilova, IL Davydkin, RK Khairetdinov, LA Rogozina

Samara State Medical University, 89 Chapaevskaya str., Samara, Russian Federation, 443099

For correspondence: Geliya Rifkatovna Gimatdinova, 89 Chapaevskaya str., Samara, Russian Federation, 443099; Tel.: +7(919)809-68-56; e-mail: gimatdinova1995@icloud.com

For citation: Gimatdinova GR, Danilova OE, Davydkin IL, et al. Current Aspects in Early Diagnosis of Cardiotoxic Complications of Drug Therapy in Oncology: A Literature Review. Clinical oncohematology. 2022;15(1):107–13. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-107-113

ABSTRACT

This analysis presents literature data, derived from open authoritative medical sources, dealing with current methods for earliest diagnosis of cardiotoxic complications, especially in the period of their subclinical manifestations. Opportunities and difficulties of diagnosing these complications are studied using the methods suggested, at the stage of subclinical myocardial dysfunction. The analysis results are presented in the form of a comparison chart covering positive aspects as well as the challenges occurring in real clinical practice. The current imaging methods showing the heart tissue condition and myocardial competence, characterize the relevant parameters more accurately. In addition to that, they enable to detect minimal changes as compared with standard 3D-echocardiography with the analysis of left ventricular ejection fraction. Therefore, many more new methods for studying cardiotoxicity should be implemented in real clinical practice.

Keywords: cardiotoxicity, PET/CT, EchoCG, myocardium, markers of cardiotoxicity, heart failure.

Received: August 5, 2021

Accepted: November 22, 2021

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REFERENCES

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Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma with Renal Impairment

AUTOIMMUNE THROMBOCYTOPENIA ,

MV Firsova, LP Mendeleeva, MV Solov’ev, DA Mironova, LA Kuzmina, VG Savchenko

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

For correspondence: Maiya Valerevna Firsova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: firs-maia@yandex.ru

For citation: Firsova MV, Mendeleeva LP, Solov’ev MV, et al. Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma with Renal Impairment. Clinical oncohematology. 2022;15(1):97–106. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-97-106

ABSTRACT

Aim. To study the efficacy and adverse event spectrum of high-dose chemotherapy with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with acute renal impairment, including hemodialysis (HD) dependence.

Materials & Methods. The retrospective single-center study enrolled 64 MM patients (30 men and 34 women) with renal impairment, aged 19–65 years (median 54 years), who received auto-HSCT in the period from 2013 to 2019. Newly diagnosed patients had a median creatinine of 462 µmol/L and a median glomerular filtration rate of 10 ml/min/1,73 m2 (CKD-EPI). HD dependence was reported in 23 (36 %) patients on diagnosis date. As a result of the induction therapy, in 13 (57 %) out of 23 patients HD could be discontinued. Prior to auto-HSCT, overall antitumor response was 91 % (complete remission was 45 %), overall renal response was 80 % (complete renal response was 28 %). In the course of auto-HSCT 10 patients remained HD dependent. Two groups were analyzed: “HD–” (program HD-independent patients during auto-HSCT, n = 54) and “HD+” (program HD-dependent recipients of auto-HSCT, n = 10).

Results. Herpes virus infection reactivation and reversible toxic encephalopathy were observed significantly more often in “HD+” than in “HD–” group (30 % vs. 6 %, p = 0.04 and 20 % vs. 0 %, p = 0.02, respectively). HD-dependent patients required red blood cell transfusion significantly more often than HD-independent patients (100 % vs. 35 % of cases; p = 0.0001). In 100 days after auto-HSCT, overall antitumor response increased from 91 % to 96 %, the rate of complete remission increased from 45 % to 64 %. After auto-HSCT the rate of complete renal response increased from 28 % to 34 %, however, overall renal response remained within the range of 80 %. After auto-HSCT, in a single case HD was discontinued. As a result of the treatment, 14 (61 %) patients became HD-independent. Transplantation-associated mortality was not reported. During median follow-up of 48 months, 5-year overall survival was 70 % and 5-year disease-free survival was 42 %.

Conclusion. Auto-HSCT is a feasible, safe, and effective treatment of MM patients with acute renal impairment. Induction therapy with subsequent auto-HSCT resulted in less need for HD which was 36 % at MM onset and 14 % on completing the treatment.

Keywords: multiple myeloma, auto-HSCT, hemodialysis, acute renal impairment, cast nephropathy.

Received: July 8, 2021

Accepted: November 28, 2021

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REFERENCES

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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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