multiple myeloma

Stratification of Patients with Multiple Myeloma: State-of-the-Art and Prospects

AUTOIMMUNE THROMBOCYTOPENIA ,

AYu Aksenova1, AS Zhuk2, EI Stepchenkova1,3, SV Gritsaev4

1 Saint Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

2 ITMO National Research University, 49 lit. A Kronverkskii pr-t, Saint Petersburg, Russian Federation, 197101

3 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

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

For correspondence: Anna Yurevna Aksenova, PhD in Biology, 17 Botanicheskaya ul., Saint Petersburg, Russian Federation, 198504; Tel.: +7(812)428-40-09; e-mail: a.aksenova@spbu.ru; Sergei Vasilevich Gritsaev, MD, PhD, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-54-68; e-mail: gritsaevsv@mail.ru

For citation: Aksenova AYu, Zhuk AS, Stepchenkova EI, Gritsaev SV. Stratification of Patients with Multiple Myeloma: State-of-the-Art and Prospects. Clinical oncohematology. 2022;15(3):259–70. (In Russ).

DOI: 10.21320/2500-2139-2022-15-3-259-270

ABSTRACT

In recent years, there has been a substantial progress in improving progression-free survival (PFS) and quality of life of multiple myeloma (MM) patients. This has become possible through implementation of novel drugs into clinical practice which were developed on the basis of multiomic molecular genetic studies in MM. The results of these studies also enabled to assess genetic heterogeneity of tumor cells in MM. That allowed to identify types and prevalence of single-nucleotide variations, structural chromosomal aberrations, and abnormal copy numbers of chromosomes in the genome of malignant plasma cells. It was shown that MM patients can have quite different spectra of detected genetic defects in the tumor. High genetic disease heterogeneity is one of the major causes of differences in drug efficacy and PFS. The present review comprehensively discusses the value of some chromosomal aberrations in risk stratification of MM patients. It describes the most prevalent aberrations, also those associated with high and low risk of early MM progression which have already been included in different international prognostic scores. Besides, the additional aberrations were determined which are potentially applicable in clinical practice. Special attention was paid to risk assessment in case a number of different chromosome rearrangements are identified in a patient. The review outlines challenges and prospects of dealing with the information on chromosome rearrangements in choosing the most optimal treatment strategy and assessing of its efficacy. In this context, emphasis is laid on integrating genetic data and such clinical parameters as age, comorbidity, renal failure, bone lesions, indications for autologous hematopoietic stem cell transplantation, etc.

Keywords: multiple myeloma, international staging systems, chromosome rearrangements, R-ISS, R2-ISS, mSMART, MASS.

Received: March 28, 2022

Accepted: June 5, 2022

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Quality of Life and Efficacy of Triplet IxaRd Therapy in Relapsed/Refractory Multiple Myeloma: Results of a Multi-Center Pilot Real-World Study

AUTOIMMUNE THROMBOCYTOPENIA ,

TI Ionova1,2, OYu Vinogradova3,4,5, YuB Kochkareva3, EE Markova3, KD Kaplanov6, MN Shirokova6,7, TV Shelekhova8, AN Levanov8, AV Kopylova9, OYu Li10, TA Mitina11, OA Rukavitsyn12, PI Simashova12, LV Anchukova13, EN Babich14, SA Volkova15, DB Dasheeva16, MV Demchenkova17, SK Dubov18, TV Esenina19, LE Ivanova17, TL Kravchuk20, EV Rimashevskaya21, MT Savinova22, NO Saraeva23, NM Porfirieva1, TP Nikitina1,2, VV Ptushkin3

1 Multinational Center for Quality of Life Research, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014

2 Saint Petersburg State University Hospital, 154 Fontanki nab., Saint Petersburg, Russian Federation, 198103

3 Moscow Municipal Center for Hematology, SP Botkin City Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

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

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

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

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

8 VI Razumovskii Saratov State Medical University, 112 Bolshaya Kazach’ya ul., Saratov, Russian Federation, 410012

9 Lipetsk Municipal Hospital No. 3 “Svobodnyi sokol”, 10 Ushinskogo ul., Lipetsk, Russian Federation, 398007

10 Sakhalin Regional Clinical Hospital, 430 Mira pr-t, Yuzhno-Sakhalinsk, Russian Federation, 693004

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

12 NN Burdenko Main Military Clinical Hospital, 3 Gospital’naya pl., Moscow, Russian Federation, 105094

13 Vologda Regional Clinical Hospital, 17 Lechebnaya ul., Vologda, Russian Federation, 160002

14 Yugry District Clinical Hospital, 40 Kalinina ul., Khanty-Mansiisk, Russian Federation, 628011

15 Privolzhsky Research Medical University, 10/1 Minina i Pozharskogo pl., Nizhny Novgorod, Russian Federation, 603005

16 Zabaikalsky Krai Oncology Dispensary, 104 Leningradskaya ul., Chita, Russian Federation, 672027

17 Irkutsk Regional Cancer Center, 32 Frunze ul., Irkutsk, Russian Federation, 664035

18 Krai Clinical Hospital No. 2, 55 Russkaya ul., Vladivostok, Russian Federation, 690105

19 Amurskaya Regional Clinical Hospital, 26 Voronkova ul., Blagoveshchensk, Russian Federation, 675000

20 Tomsk National Research Medical Center, 5 Kooperativnyi per., Tomsk, Russian Federation, 634009

21 Russian Medical Academy of Postgraduate Education, 38 Smolnaya ul., Moscow, Russian Federation, 125445

22 Municipal Clinical Hospital No. 16, 121 Gagarina ul., Kazan, Russian Federation, 420039

23 Irkutsk Regional Clinical Hospital, 100 Yubileinyi mikroraion, Irkutsk, Russian Federation, 664049

For correspondence: Tatyana Pavlovna Nikitina, MD, PhD, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014; Tel.: +7(962)710-17-12; e-mail: qolife@mail.ru

For citation: Ionova TI, Vinogradova OYu, Kochkareva YuB, et al. Quality of Life and Efficacy of Triplet IxaRd Therapy in Relapsed/Refractory Multiple Myeloma: Results of a Multi-Center Pilot Real-World Study. Clinical oncohematology. 2022;15(3):240–52. (In Russ).

DOI: 10.21320/2500-2139-2022-15-3-240-252

ABSTRACT

Aim. To study quality of life (QoL) indicators and symptom profile as well as treatment satisfaction of patients with relapsed/refractory multiple myeloma (r/r MM) on triplet therapy based on ixazomib combined with lenalidomide and dexamethasone (IxaRd); to assess efficacy and safety of IxaRd protocol in real-world clinical practice.

Materials & Methods. The study enrolled 40 patients with confirmed r/r MM diagnosis, aged > 18 years, at 18 Russian health care institutions. They received at least one line of prior therapy and were IxaRd-eligible. Clinical and QoL indicators were assessed according to the RAND SF-36, and symptoms were evaluated using the ESAS-R questionnaire prior to IxaRd therapy and in 1, 3, 6, 9, 12, 15, and 18 months after its start. Besides, patients filled out checklists for assessment of treatment satisfaction at all time-points after therapy onset. The analysis of clinical IxaRd efficacy included assessment of treatment response by IMWG 2011 criteria, as well as response duration, overall survival (OS), and progression-free survival (PFS). The analysis of IxaRd safety was based on reporting adverse events (AEs), including severe ones (SAEs). To analyze patient-reported QoL and symptom changes during follow-up, GEE was used. To determine clinically meaningful changes, an effect size was calculated.

Results. The study included 40 r/r MM patients (mean age 63 ± 9 years, 65 % women). Median disease duration before IxaRd therapy onset was 55 months (range 2–99 months). 60 % of patients had IIIA/IIIB Durie-Salmon stage. With the median IxaRd duration of 7.5 months, clinical benefit rate was 71.8 %. Complete response was reported in 7.7 % of patients, stringent complete response in 2.6 % of patients, very good partial response in 5.1 % of patients, partial response in 30.8 % of patients, and minor response was achieved in 25.6 % of patients. Stable disease was reported in 15.4 % of patients, and disease progression was identified in 10.3 % patients, including immunochemical relapse in 1 patient. The median response duration was 16.3 months (95% confidence interval [95% CI] 15.4–17.3 months), the median PFS was 10.6 months (95% CI 6.3–16.3 months). The median OS was not reached; the 1-year OS after IxaRd therapy onset was 85.2 % (95% CI 71–99 %). AEs on IxaRd therapy were reported in 55 % of patients, SAEs were reported in 3 (7.5 %) patients. Positive QoL changes were observed on IxaRd therapy. QoL improvement was meaningful in terms of physical functioning, role-physical functioning, general health, vitality, and mental health, compared to baseline. Moreover, a considerable decrease of pain, fatigue, and nausea was revealed. On the whole, 87.5 % of patients were satisfied with the triplet IxaRd therapy.

Conclusion. The results of the present pilot study demonstrate efficacy and safety of the triplet IxaRd therapy (all per os) in real-world clinical practice from r/r MM patients’ and physicians’ perspective. Our data testify to the importance of patients’ feedback in the evaluation of therapy efficacy.

Keywords: multiple myeloma, relapsed/refractory, ixazomib, quality of life, real-world clinical practice.

Received: March 16, 2022

Accepted: June 6, 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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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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Molecular Profiling and Minimal Residual Disease Monitoring in Multiple Myeloma Patients: A Literature Review

AUTOIMMUNE THROMBOCYTOPENIA

AV Semyanikhina1,2, EE Tolstykh1

1 NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 NP Bochkov Research Centre for Medical Genetics, 1 Moskvorech’e str., Moscow, Russian Federation, 115522

For correspondence: Aleksandra Vladimirovna Semyanikhina, MD, PhD, 23 Kashirskoye sh., Moscow, Russian Federation, Российская Федерация, 115478; Tel.: +7(926)371-21-56; e-mail: alexandra_silina@mail.ru

For citation: Semyanikhina AV, Tolstykh EE. Molecular Profiling and Minimal Residual Disease Monitoring in Multiple Myeloma Patients: A Literature Review. Clinical oncohematology. 2021;14(4):436–43. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-436-443

ABSTRACT

A personalized approach is a promising tool for malignant neoplasm (MN) treatment. Gaining success and benefit assessment of this approach were considerably facilitated by the implementation of the new generation sequencing techniques which allow to obtain comprehensive information on the tumor genome and transcriptome state with identifying potential biomarkers and targets for directed drug action. Despite the exponential growth in the number of sequenced tumor genomes, some of them are not subject of active clinical studies, although obviously and increasingly require optimization of current treatment regimens. One of these pathologies is multiple myeloma (MM). Considerable advances in its diagnosis and treatment have substantially increased survival rates. However, MM cannot be removed from the list of fatal diseases, yet. It is a neoplasm which needs to be further studied and explored for implementation of new treatment strategies, most of which would be based on pheno- and genotypic characteristics of tumor cells. The present review deals with the state of the art in the study of the MM molecular genetic profile, minimal residual disease (MRD) monitoring as well as potentials of the new generation sequencing for MRD diagnosis, prognosis, estimation, and search for predictors aimed at chemotherapy optimization.

Keywords: multiple myeloma, new generation sequencing, minimal residual disease.

Received: May 21, 2021

Accepted: August 29, 2021

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Infectious Complications in Multiple Myeloma under Current Epidemiological Conditions: A Literature Review

AUTOIMMUNE THROMBOCYTOPENIA ,

IL Davydkin, EV Mordvinova, TP Kuzmina

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

For correspondence: Elizaveta Vladimirovna Mordvinova, 89 Chapaevskaya str., Samara, Russian Federation, 443099; Tel.: +7(917)037-52-10, e-mail: liza.mordvinova.94@mail.ru

For citation: Davydkin IL, Mordvinova EV, Kuzmina TP. Infectious Complications in Multiple Myeloma under Current Epidemiological Conditions: A Literature Review. Clinical oncohematology. 2021;14(3):386–90. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-386-390

ABSTRACT

The review outlines current views on immune system in multiple myeloma (MM) and the basic pathogens inducing infectious complications in such patients. Although in recent years there has been considerable progress in studying molecular mechanisms of the MM development (pathogenesis), methods of its diagnosis, treatment, and prediction of outcomes, one of the main causes of death within this group of patients is infectious complications. In this context, it would be relevant to further study immune disorders and the spectrum of infectious pathogens common in the MM patient cohort. The study and correction of immunological status can contribute to improving the MM outcomes, which in turn will lead to increased life expectancy.

Keywords: multiple myeloma, immunological status, infectious complications, COVID-19.

Received: March 12, 2021

Accepted: June 8, 2021

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REFERENCES

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Multiple Myeloma and Dendritic Cell Vaccines

AUTOIMMUNE THROMBOCYTOPENIA ,

IV Gribkova, AA Zavyalov

Research Institute for Healthcare Organization and Medical Management, 9 Sharikopodshipnikovskaya str., Moscow, Russian Federation, 115088

For correspondence: Irina Vladimirovna Gribkova, PhD in Biology, 9 Sharikopodshipnikovskaya str., Moscow, Russian Federation, 115088; Tel.: +7(916)078-73-90; e-mail: igribkova@yandex.ru

For citation: Gribkova IV, Zavyalov AA. Multiple Myeloma and Dendritic Cell Vaccines. Clinical oncohematology. 2021;14(3):370–7. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-370-377

ABSTRACT

Despite advances in the treatment of multiple myeloma, most of patients after its completion retain minimal residual disease (MRD-positive status), which increases the risk of relapse. Antigen-specific immunotherapy of tumors contributes to improving the clinical outcomes in such patients by the killing of cancer drug resistant clone of tumor cells without any damage to normal tissues. Dendritic cells (DC) are antigen-presenting elements with the main function of antigen-capturing, processing, and presenting them to naive T-lymphocytes for the activation of immune response against the captured antigen. The unique ability of DC to activate T-helpers and cytotoxic T-lymphocytes as well as to target thereby the immune reactions was used in developing DC-based tumor immunotherapy. This approach suggests the implementation of the so-called ‘DC-vaccines’. The clinical trials performed by now also showed the results of using DC-vaccines in various tumors including hematological ones. On the whole, according to the studies DC-vaccines are characterized by satisfactory safety profile, moderate immunological activity, and moderate clinical efficacy. The present review provides the results of clinical trials dealing with the use of DC-based vaccines in multiple myeloma patients. Besides, the potentials of improving the clinical efficacy of this therapy are discussed.

Keywords: multiple myeloma, dendritic cells, DC-vaccines, hematological malignancies, immunotherapy.

Received: March 9, 2021

Accepted: June 11, 2021

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Статистика Plumx английский

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Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation

AUTOIMMUNE THROMBOCYTOPENIA , ,

SP Svitina, ZhYu Sidorova, II Kostroma, AA Zhernyakova, AV Chechetkin, ZhV Chubukina, SV Gritsaev, SI Kapustin, SS Bessmeltsev

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

For correspondence: Svetlana Pavlovna Svitina, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; e-mail: shvetikova@gmail.com

For citation: Svitina SP, Sidorova ZhYu, Kostroma II, et al. Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(3):340–6. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-340-346

ABSTRACT

Aim. To assess polymorphism value of interleukins (IL6, IL1B, IL10) and tumor necrosis factor α (TNF) genes in multiple myeloma (MM) patients who received autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The study enrolled 37 MM patients (15 men and 22 women) aged 38–66 years (mean age 54.5 ± 6.4 years), who received auto-HSCT. After transplantation, partial (PR), very good partial (VGPR), and complete (CR) responses were reported in 11, 7, and 19 patients, respectively. In 23 (62.2 %) patients CD34+ cell collection on the day of the first leukocytapheresis session exceeded the suboptimal level of 2.5 × 106/kg. The control group included 236 healthy subjects. Genotyping by PCR with subsequent analysis of restriction fragment length polymorphism of amplified products was performed. To identify between-group differences in genotype distribution, Fisher’s exact test with measurements of odds ratio (OR) and р–value was used.

Results. The study group of patients was distinguished from the control group by more than twofold increased proportion of homozygous IL1B –31C (OR 2.7; p = 0.029). The proportion of heterozygous –174G/C allelic variant of IL6 gene in the subgroup of patients with CR after auto-HSCT was considerably higher than in patients with VGPR and PR (OR 5.6; p = 0.022). In the subgroup of patients with CD34+ cell collection > 2.5 × 106/kg the proportion of those with IL10 –592C/C genotype was twice as high as in patients with lower CD34+ cell collection (OR 3.9; p = 0.091).

Conclusion. The present study confirms the relationship of –31C/Т polymorphism in IL1B gene in homozygous state with higher MM risk. It proved the association of –174G/C polymorphism in IL6 gene and –592C/A polymorphism in IL10 gene with the chosen criteria for auto-HSCT efficacy. To precisely clarify the value of variants in the above genes for predicting chemotherapy effect in MM, further studies involving more patients are required.

Keywords: multiple myeloma, genes polymorphism, immune response, cytokines, autologous hematopoietic stem cell transplantation.

Received: March 4, 2021

Accepted: June 10, 2021

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Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

AUTOIMMUNE THROMBOCYTOPENIA ,

II Kostroma1, ZhYu Sidorova1, NYu Semenova1, AA Zhernyakova1, RR Sabitova1, SP Svitina1, EI Stepchenkova2,3, SS Bessmeltsev1, AV Chechetkin1, SV Gritsaev1

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

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

3 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Sidorova ZhYu, Semenova NYu, et al. Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2021;14(3):333–9. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-333-339

ABSTRACT

Aim. To assess the rate of cases without antitumor response quality improvement after high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM). To assess the rate of allelic variants of IL1B, IL6, IL10, TNF genes and the status of hematopoietic niche cells as potential predictors of auto-HSCT efficacy.

Materials & Methods. A retrospective analysis was based on the data of 84 MM patients who received 112 auto-HSCTs, including 84 first and 28 repeated courses. Response variants were estimated according to IWG criteria. Molecular profiling of IL1B, IL6, IL10, and TNF genes was performed using polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length polymorphism of PCR products. To analyze the status of hematopoietic niche cells histological, immunohistochemical, and morphometric methods were applied.

Results. The first auto-HSCT yielded response quality improvement in 29 (54.7 %) out of 84 patients. The rate of complete response was significantly higher in patients who showed very good partial response before HDCT with auto-HSCT, than in patients with partial response (PR), i.e., 57.9 % and 18.2 %, respectively (р = 0.005). No differences were identified in the groups of patients with other clinical and hematological parameters. After the second auto-HSCT in 4 out of 6 patients with PR the response variant did not change. A significant decrease of MM activity was associated with IL6 (–174С) mutant allele carrier status of 81.3 % vs. 41.6 % in the group with the unchanged response variant (р = 0.05). Response quality improvement was also related to a large number of cells on the endosteum in histological specimens of bone marrow (р = 0.038).

Conclusion. The carrier status of IL6 (–174С) pathologic allele as well as the number of cells on the endosteum in histological specimens of bone marrow can be regarded as predictors of response quality improvement or lack thereof in MM patients after auto-HSCT.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, IL6 gene, hematopoietic niche.

Received: January 29, 2021

Accepted: May 30, 2021

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Obesity as a Poor Prognostic Factor in Multiple Myeloma

AUTOIMMUNE THROMBOCYTOPENIA ,

ES Mikhailov1, GN Salogub1, SS Bessmeltsev2

1 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

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

For correspondence: Evgenii Sergeevich Mikhailov, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(812)702-37-49; e-mail: mikhailov_md@bk.ru

For citation: Mikhailov ES, Salogub GN, Bessmeltsev SS. Obesity as a Poor Prognostic Factor in Multiple Myeloma. Clinical oncohematology. 2021;14(3):315–20. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-315-320

ABSTRACT

Aim. To assess the impact of obesity and overweight on the outcomes of multiple myeloma (MM) treatment.

Materials & Methods. The present retrospective study enrolled 214 patients with newly diagnosed MM. The median age was 59 years (range 29–89 years), male patients accounted for 40.2 %. The analysis focused on complication incidence, overall survival, and time to the second-line therapy depending on body mass index (BMI) at disease onset.

Results. In the groups of patients with BMI > 35 kg/m2 and BMI ≤ 35 kg/m2 the median overall survival was 42 and 95 months, respectively (hazard ratio [HR] 0.17; 95% confidence interval [95% CI] 0.08–0.37; p < 0.05). In the group of patients with obesity ≥ grade 2 the median time to the second-line therapy was 25 months, being less than in the group of patients with BMI ≤ 35 kg/m2 (43 months; HR 0.58; 95% CI 0.31–0.99; p < 0.05). As a result of therapy, the incidence of corticosteroid-associated hyperglycemia and infectious complications as well as the rate of delayed initiation of the next cycle and dose reduction of anticancer drugs were significantly higher in patients with BMI > 35 kg/m2 (p < 0.05).

Conclusion. Obesity ≥ grade 2 is a poor prognostic factor for complications and is associated with diminishing outcomes of ММ treatment. Accompanying morbid obesity leads to a higher incidence of therapy complications longer intervals between chemotherapy courses and drug dose reduction.

Keywords: multiple myeloma, obesity, prognosis, survival.

Received: March 9, 2021

Accepted: June 15, 2021

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Статистика Plumx английский

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