Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-407-412
Гелия Рифкатовна Гиматдинова, О. Е. Данилова, В. П. Кузьмин, Г. И. Давыдкин, Ю. В. Косталанова, Д. А. Кудлай, И. Л. Давыдкин
In clinical oncology in general, tumor treatment is closely related to a highly relevant issue of chemotherapy-induced adverse events. Among side effects, cardiovascular toxicity occupies the foremost place. The strategy of controlling the cardiovascular complications associated with antitumor drug and cell therapies presupposes an early diagnosis of changes in the heart muscle and blood vessels at the stage of subclinical manifestations of adverse events. The present literature review provides the analysis of data on immunotherapy side effects in hematological malignancies with a focus on cardiovascular complications. The review comprehensively discusses the characteristics of cardiovascular complications associated with immune checkpoint inhibitors, CAR-T cell products, bispecific antibodies as well as immunomodulatory and antiangiogenic drugs.
{"title":"Сердечно-сосудистые осложнения иммунотерапии гематологических злокачественных опухолей (обзор литературы)","authors":"Гелия Рифкатовна Гиматдинова, О. Е. Данилова, В. П. Кузьмин, Г. И. Давыдкин, Ю. В. Косталанова, Д. А. Кудлай, И. Л. Давыдкин","doi":"10.21320/2500-2139-2023-16-4-407-412","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-407-412","url":null,"abstract":"In clinical oncology in general, tumor treatment is closely related to a highly relevant issue of chemotherapy-induced adverse events. Among side effects, cardiovascular toxicity occupies the foremost place. The strategy of controlling the cardiovascular complications associated with antitumor drug and cell therapies presupposes an early diagnosis of changes in the heart muscle and blood vessels at the stage of subclinical manifestations of adverse events. The present literature review provides the analysis of data on immunotherapy side effects in hematological malignancies with a focus on cardiovascular complications. The review comprehensively discusses the characteristics of cardiovascular complications associated with immune checkpoint inhibitors, CAR-T cell products, bispecific antibodies as well as immunomodulatory and antiangiogenic drugs.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-351-360
Анатолий Александрович Даниленко, Н. А. Фалалеева, С. В. Шахтарина
The staging of Hodgkin lymphoma lays the groundwork for optimal treatment decision making. For a long time, bone marrow assessment has been an integral part of staging. The study of bone marrow involvement in tumor progression includes radiological method and morphological analysis of its core biopsy samples. During the last five decades of using bone marrow core biopsy, the attitude of oncologists and hematologists to this invasive and painful procedure remained ambivalent between denying and affirming the need to carry it out in all or most Hodgkin lymphoma cases. The present review provides the historical background of bone marrow core biopsy and considers its appropriateness for patients with classical Hodgkin lymphoma.
{"title":"История вопроса о роли биопсии костного мозга в системе стадирования классической лимфомы Ходжкина и современный взгляд в эру ПЭТ-КТ (обзор литературы)","authors":"Анатолий Александрович Даниленко, Н. А. Фалалеева, С. В. Шахтарина","doi":"10.21320/2500-2139-2023-16-4-351-360","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-351-360","url":null,"abstract":"The staging of Hodgkin lymphoma lays the groundwork for optimal treatment decision making. For a long time, bone marrow assessment has been an integral part of staging. The study of bone marrow involvement in tumor progression includes radiological method and morphological analysis of its core biopsy samples. During the last five decades of using bone marrow core biopsy, the attitude of oncologists and hematologists to this invasive and painful procedure remained ambivalent between denying and affirming the need to carry it out in all or most Hodgkin lymphoma cases. The present review provides the historical background of bone marrow core biopsy and considers its appropriateness for patients with classical Hodgkin lymphoma.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-413-425
О. Ю. Виноградова, М. М. Панкрашкина, Анна Леонидовна Неверова, М. В. Черников, Л. А. Муха, Д. И. Шихбабаева, В. В. Птушкин
Aim. To assess the stability of clinical remission in patients with primary immune thrombocytopenia (ITP) after withdrawal of thrombopoietin receptor agonists (TPO-RAs).
Materials & Methods. The study enrolled 456 patients with primary ITP who received second- and subsequent-line TPO-RA treatment. Complete platelet response (PR) was achieved in 338 patients, the therapy was discontinued in 116 of them. The present prospective clinical study started in 2014 and focused on the data of these 116 patients. Among them, there were 27 (23 %) men and 89 (77 %) women. By the time of TPO-RA therapy onset, the median age of the patients was 60 years (range 13–87 years), on ITP diagnosis date it was 52 years (range 1–80 years).
Results. By the time of data analysis, 59 % of patients sustained PR after TPO-RA withdrawal. The median PR duration after TPO-RA withdrawal was 230 weeks. Romiplostim and eltrombopag recipients showed no significant differences in the survival rates without PR-loss after TPO-RA withdrawal. In the present study, the maximum PR duration achieved 9.5 years. The mid-term assessment of PR status was carried out in 3, 6, 12, 24, and 30 months after TPO-RA withdrawal and showed 99 %, 94 %, 83 %, 72 %, and 70 %, respectively. The number of previous therapy lines significantly affected the survival rates without PR-loss (p = 0.011). The age of patients, prior splenectomy, TPO-RA treatment duration, time to different PR levels on therapy, PR duration on TPO-RA therapy, and platelet count upon TPO-RA withdrawal showed no significant effect on this parameter. After PR-loss, TPO-RAs were administered again to 31 (27 %) patients. Repeated PR was achieved in 26 (84 %) of them.
Conclusion. TPO-RA administration yields multi-year off-treatment remission in some patients with primary ITP. Upon therapy discontinuation, 59 % of patients with complete PR sustained PR for 3 months to 9.5 years. Stable PR after TPO-RA withdrawal significantly correlated with only one of the studied prognostic parameters, i.e., the number of previous therapy lines.
{"title":"Primary Immune Thrombocytopenia and Thrombopoietin Receptor Agonists: Feasibilities of Treatment Discontinuation upon Achieving Stable Complete Platelet Response","authors":"О. Ю. Виноградова, М. М. Панкрашкина, Анна Леонидовна Неверова, М. В. Черников, Л. А. Муха, Д. И. Шихбабаева, В. В. Птушкин","doi":"10.21320/2500-2139-2023-16-4-413-425","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-413-425","url":null,"abstract":"Aim. To assess the stability of clinical remission in patients with primary immune thrombocytopenia (ITP) after withdrawal of thrombopoietin receptor agonists (TPO-RAs).
 Materials & Methods. The study enrolled 456 patients with primary ITP who received second- and subsequent-line TPO-RA treatment. Complete platelet response (PR) was achieved in 338 patients, the therapy was discontinued in 116 of them. The present prospective clinical study started in 2014 and focused on the data of these 116 patients. Among them, there were 27 (23 %) men and 89 (77 %) women. By the time of TPO-RA therapy onset, the median age of the patients was 60 years (range 13–87 years), on ITP diagnosis date it was 52 years (range 1–80 years).
 Results. By the time of data analysis, 59 % of patients sustained PR after TPO-RA withdrawal. The median PR duration after TPO-RA withdrawal was 230 weeks. Romiplostim and eltrombopag recipients showed no significant differences in the survival rates without PR-loss after TPO-RA withdrawal. In the present study, the maximum PR duration achieved 9.5 years. The mid-term assessment of PR status was carried out in 3, 6, 12, 24, and 30 months after TPO-RA withdrawal and showed 99 %, 94 %, 83 %, 72 %, and 70 %, respectively. The number of previous therapy lines significantly affected the survival rates without PR-loss (p = 0.011). The age of patients, prior splenectomy, TPO-RA treatment duration, time to different PR levels on therapy, PR duration on TPO-RA therapy, and platelet count upon TPO-RA withdrawal showed no significant effect on this parameter. After PR-loss, TPO-RAs were administered again to 31 (27 %) patients. Repeated PR was achieved in 26 (84 %) of them.
 Conclusion. TPO-RA administration yields multi-year off-treatment remission in some patients with primary ITP. Upon therapy discontinuation, 59 % of patients with complete PR sustained PR for 3 months to 9.5 years. Stable PR after TPO-RA withdrawal significantly correlated with only one of the studied prognostic parameters, i.e., the number of previous therapy lines.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-426-448
Максим Валерьевич Соловьев, М. В. Соловьева, Л. П. Менделеева
Supportive therapy is becoming increasingly important for the state-of-the-art algorithm of multiple myeloma (MM) treatment. The introduction of innovative drugs and transplantation methods into clinical practice considerably improved the disease-free and overall survival rates. However, in the vast majority of cases, MM still remains an incurable malignant plasma cell tumor. It is often treated on a continuous basis with a succession of targeted drugs and integration of glucocorticosteroids and conventional cytostatic agents into the program therapy. All of these together with immunodeficiency, bone lesions, and myeloma nephropathy lead to a high risk of adverse events and cumulative toxicity of treatment. At the same time, one of the main goals at all MM therapy stages is to maintain quality of life. The characteristics of clinical symptoms, the nuances of targeted therapy and chemotherapy-associated adverse events justify the need for further development of supportive MM therapy algorithms which remain to be a matter of current concern. They should be mainly aimed at preventing the therapy complications, reducing the rate of adverse events and clinical manifestations of side effects as well as developing a treatment strategy for cumulative toxicity. In the state-of-the-art algorithm of program MM treatment, supportive therapy-related knowledge is of no less value than the information on antitumor drugs and their efficacy. This paper reports the personal experience and provides recommendations mostly based on the results of clinical studies or views of expert panels. It also offers practical recommendations for supportive therapy in symptomatic MM which include prevention of skeletal complications, thromboses, and infections, nausea and vomiting management, vaccination, pre-medication and the algorithm of monoclonal antibody administration, anesthesia, peripheral polyneuropathy treatment, correction of secondary immunodeficiency, nutritional support, fatigue assessment and countermeasures.
{"title":"Сопроводительная терапия при множественной миеломе: практические рекомендации","authors":"Максим Валерьевич Соловьев, М. В. Соловьева, Л. П. Менделеева","doi":"10.21320/2500-2139-2023-16-4-426-448","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-426-448","url":null,"abstract":"Supportive therapy is becoming increasingly important for the state-of-the-art algorithm of multiple myeloma (MM) treatment. The introduction of innovative drugs and transplantation methods into clinical practice considerably improved the disease-free and overall survival rates. However, in the vast majority of cases, MM still remains an incurable malignant plasma cell tumor. It is often treated on a continuous basis with a succession of targeted drugs and integration of glucocorticosteroids and conventional cytostatic agents into the program therapy. All of these together with immunodeficiency, bone lesions, and myeloma nephropathy lead to a high risk of adverse events and cumulative toxicity of treatment. At the same time, one of the main goals at all MM therapy stages is to maintain quality of life. The characteristics of clinical symptoms, the nuances of targeted therapy and chemotherapy-associated adverse events justify the need for further development of supportive MM therapy algorithms which remain to be a matter of current concern. They should be mainly aimed at preventing the therapy complications, reducing the rate of adverse events and clinical manifestations of side effects as well as developing a treatment strategy for cumulative toxicity. In the state-of-the-art algorithm of program MM treatment, supportive therapy-related knowledge is of no less value than the information on antitumor drugs and their efficacy. This paper reports the personal experience and provides recommendations mostly based on the results of clinical studies or views of expert panels. It also offers practical recommendations for supportive therapy in symptomatic MM which include prevention of skeletal complications, thromboses, and infections, nausea and vomiting management, vaccination, pre-medication and the algorithm of monoclonal antibody administration, anesthesia, peripheral polyneuropathy treatment, correction of secondary immunodeficiency, nutritional support, fatigue assessment and countermeasures.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"50 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-399-406
Екатерина Георгиевна Хамаганова, С. П. Хижинский, Е. П. Кузьминова, А. Р. Абдрахимова, Е. А. Леонов, Т. В. Гапонова, Е. Н. Паровичникова
Background. HLA-typing and matched donor selection as well as the detection of donor-specific anti-HLA antibodies are essential for allogeneic hematopoietic cell transplantation (allo-HSCT). In accordance with the guidelines of the Center for International Blood and Marrow Transplant Research (CIBMTR) optimal HLA-typing is performed on 11 HLA genes (-A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1, and ‐DPB1) with an adequate coverage aiming to obtain the values at the two-field level.
Aim. To assess the results of multi-locus HLA-typing in bone marrow/hematopoietic cell donors from the database at the National Research Center for Hematology in terms of their conformance with the CIBMTR guidelines for allo-HSCT and to analyze the frequency and distribution of HLA alleles and multi-locus HLA haplotypes.
Materials & Methods. The study enrolled 3485 donors who were HLA-typed by next-generation sequencing.
Results. In all donors, the alleles of HLA class I genes were identified at the fourth-field level (nucleotide sequence). When the results were reduced to the second-field level (amino acid sequence), 61 HLA-A, 92 HLA-B, and 49 HLA-C alleles were detected. The alleles of class II genes were discovered either at the two-field or high-resolution levels. Among the HLA-DRB locus genes, 57 DRB1, 11 DRB3, 6 DRB4, and 5 DRB5 alleles were identified. Also, 23 HLA-DQA1, 30 HLA-DQB1, 14 HLA-DPA1, and 33 HLA-DPB1 alleles were detected. There were reported 3289 different HLA haplotypes of A-B-C-DRB1-DQA1-DQB1-DPA1-DPB1 genes.
Conclusion. The database created at the National Research Center for Hematology includes potential bone marrow/hematopoietic stem cell donors typed for 11 classical polymorphic genes HLA-A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1, and -DPB1, which is in line with the guidelines of CIBMTR. The frequency and distribution of HLA alleles and multi-locus HLA haplotypes in our donors correspond to those in populations of European origin. HLA-typing and donor selection with regard to 11 HLA genes will contribute to improving the outcomes of both unrelated and haploidentical HSCTs.
{"title":"An Optimal Multi-Locus HLA-Typing in Potential Donors of Allogeneic Hematopoietic Stem Cells","authors":"Екатерина Георгиевна Хамаганова, С. П. Хижинский, Е. П. Кузьминова, А. Р. Абдрахимова, Е. А. Леонов, Т. В. Гапонова, Е. Н. Паровичникова","doi":"10.21320/2500-2139-2023-16-4-399-406","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-399-406","url":null,"abstract":"Background. HLA-typing and matched donor selection as well as the detection of donor-specific anti-HLA antibodies are essential for allogeneic hematopoietic cell transplantation (allo-HSCT). In accordance with the guidelines of the Center for International Blood and Marrow Transplant Research (CIBMTR) optimal HLA-typing is performed on 11 HLA genes (-A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1, and ‐DPB1) with an adequate coverage aiming to obtain the values at the two-field level.
 Aim. To assess the results of multi-locus HLA-typing in bone marrow/hematopoietic cell donors from the database at the National Research Center for Hematology in terms of their conformance with the CIBMTR guidelines for allo-HSCT and to analyze the frequency and distribution of HLA alleles and multi-locus HLA haplotypes.
 Materials & Methods. The study enrolled 3485 donors who were HLA-typed by next-generation sequencing.
 Results. In all donors, the alleles of HLA class I genes were identified at the fourth-field level (nucleotide sequence). When the results were reduced to the second-field level (amino acid sequence), 61 HLA-A, 92 HLA-B, and 49 HLA-C alleles were detected. The alleles of class II genes were discovered either at the two-field or high-resolution levels. Among the HLA-DRB locus genes, 57 DRB1, 11 DRB3, 6 DRB4, and 5 DRB5 alleles were identified. Also, 23 HLA-DQA1, 30 HLA-DQB1, 14 HLA-DPA1, and 33 HLA-DPB1 alleles were detected. There were reported 3289 different HLA haplotypes of A-B-C-DRB1-DQA1-DQB1-DPA1-DPB1 genes.
 Conclusion. The database created at the National Research Center for Hematology includes potential bone marrow/hematopoietic stem cell donors typed for 11 classical polymorphic genes HLA-A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1, and -DPB1, which is in line with the guidelines of CIBMTR. The frequency and distribution of HLA alleles and multi-locus HLA haplotypes in our donors correspond to those in populations of European origin. HLA-typing and donor selection with regard to 11 HLA genes will contribute to improving the outcomes of both unrelated and haploidentical HSCTs.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-380-386
Валерия Витальевна Лозовая, О. А. Малихова, А. О. Туманян
Aim. To characterize the main differentially significant endoscopic features specific to the gastritis-like form of primary gastric non-Hodgkin lymphomas (NHL).
Materials & Methods. This prospective study analyzes the results of complex endoscopic diagnosis in 43 patients with primary gastric NHL. They were examined and treated at the NN Blokhin National Medical Cancer Research Center from 2019 to 2023. The patients were 30–70 years of age, those over the age of 50 predominated and accounted for 79 % (n = 34). There were 33 women and 10 men. The control group included 45 patients with gastritis-like malignant gastric tumors: adenocarcinoma and signet-ring cell cancer.
Results. The morphological analysis yielded a diagnosis of MALT-lymphoma in 90.7 % (n = 39) and diffuse large B-cell lymphoma in 9.3 % (n = 4) of cases. Sensitivity, specificity, and accuracy of the clarification methods of complex endoscopic diagnosis were considerably higher compared to white-light mode examination. According to the results of complex endoscopic analysis, all patients were stratified into 4 groups with different types of H. pylori-induced atrophic gastritis (n = 10; 23.25 %), erosive gastritis (n = 10; 23.25 %), hyperplastic gastritis (n = 8; 18.6 %), and combined gastritis (n = 15; 34.9 %). The focus was laid on identifying the main differentially significant endoscopic features specific to the gastritis-like form of primary gastric NHL which distinguish it from the lesions in other malignant tumors.
Conclusion. The complex examination using 4 concrete clarification methods of endoscopic diagnosis is indispensable to properly interpret the detected changes and timely diagnose the gastritis-like form of primary gastric NHL. These include narrow-band imaging (NBI/BLI and LCI), close-focus and magnification examinations, combined narrow-band imaging and magnification examination, as well as endosonography.
{"title":"Эндоскопическая семиотика гастритоподобной формы первичных неходжкинских лимфом желудка","authors":"Валерия Витальевна Лозовая, О. А. Малихова, А. О. Туманян","doi":"10.21320/2500-2139-2023-16-4-380-386","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-380-386","url":null,"abstract":"Aim. To characterize the main differentially significant endoscopic features specific to the gastritis-like form of primary gastric non-Hodgkin lymphomas (NHL).
 Materials & Methods. This prospective study analyzes the results of complex endoscopic diagnosis in 43 patients with primary gastric NHL. They were examined and treated at the NN Blokhin National Medical Cancer Research Center from 2019 to 2023. The patients were 30–70 years of age, those over the age of 50 predominated and accounted for 79 % (n = 34). There were 33 women and 10 men. The control group included 45 patients with gastritis-like malignant gastric tumors: adenocarcinoma and signet-ring cell cancer.
 Results. The morphological analysis yielded a diagnosis of MALT-lymphoma in 90.7 % (n = 39) and diffuse large B-cell lymphoma in 9.3 % (n = 4) of cases. Sensitivity, specificity, and accuracy of the clarification methods of complex endoscopic diagnosis were considerably higher compared to white-light mode examination. According to the results of complex endoscopic analysis, all patients were stratified into 4 groups with different types of H. pylori-induced atrophic gastritis (n = 10; 23.25 %), erosive gastritis (n = 10; 23.25 %), hyperplastic gastritis (n = 8; 18.6 %), and combined gastritis (n = 15; 34.9 %). The focus was laid on identifying the main differentially significant endoscopic features specific to the gastritis-like form of primary gastric NHL which distinguish it from the lesions in other malignant tumors.
 Conclusion. The complex examination using 4 concrete clarification methods of endoscopic diagnosis is indispensable to properly interpret the detected changes and timely diagnose the gastritis-like form of primary gastric NHL. These include narrow-band imaging (NBI/BLI and LCI), close-focus and magnification examinations, combined narrow-band imaging and magnification examination, as well as endosonography.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-370-379
Анна Анатольевна Спорник, Н. С. Васильев, А. А. Самойлова, А. А. Мамедова, В. С. Богатырев, Е. Г. Смирнова, А. А. Банникова, А. А. Рукавицын, Н. С. Шорохов, Н. Е. Мочкин, В. О. Саржевский, Е. А. Демина, В. Я. Мельниченко
Aim. To assess the efficacy of a long-acting form of the granulocyte colony-stimulating factor (G-CSF) empegfilgrastim in primary prevention of neutropenia in patients with advanced stages of classical Hodgkin lymphoma (cHL) who received intensive chemotherapy with reduced inter-cycle interval under the protocol “LKh-Rossiya-1”.
Materials & Methods. The study enrolled 35 patients with newly diagnosed cHL. All patients had advanced stages (IIB X/Е and III/IV) of the disease. They were treated at the NI Pirogov National Medical and Surgical Center from March 2013 to August 2022. The primary prevention of neutropenia by long-acting G-CSF (empegfilgrastim) was administered to 21 patients under the protocol “LKh-Rossiya-1”. They received 6 chemotherapy cycles of modified EACODD-14, in total 126 cycles. The control group consisted of 14 patients who received 6 ЕАСОРР-14 chemotherapy cycles (in total 84 cycles) with dacarbazine as substitution for procarbazine. In the control group, the primary prevention of neutropenia was carried out using discrete G-CSF (filgrastim). The median (range) follow-up in the main (n = 21) and control (n = 14) groups was 18 (5–36) and 39 (29–116) months, respectively. The treatment efficacy was assessed based on PET-CT in 31 patients and on CT in 4 patients.
Results. By the end of chemotherapy, complete metabolic response was achieved in 28 (80 %) out of 35 patients (95 % in the EACODD-14 and 73 % in ЕАСОРР-14 groups). In 6 (17 %) patients, partial remission was confirmed only by CT scan, and in 1 (3 %) patient, PET/CT showed stabilization. After consolidation radiotherapy, complete remission was reported in all 35 patients. Both groups received the full chemotherapy program per protocol. Without a violation of G-CSF regimen, the EACODD-14 group received 121 (96 %) cycles out of those 126 planned, whereas the ЕАСОРР-14 group received all 84 cycles per protocol. Full implementation of 107 (88.4 %) cycles in the first group and 24 (29 %) cycles in the second group was achieved in 12 (57 %) and 5 (36 %) patients, respectively (p < 0.001). Neutropenia grade 4 was more often identified in filgrastim than in empegfilgrastim recipients (57 % vs. 19 %; p < 0.05) and in a larger number of cycles (15 % vs. 3 %; p < 0.01). The rate of infection episodes in the ЕАСОРР-14 group was higher (50 % vs. 28 %) and in more cycles (15 % vs. 5 %; p < 0.05). Due to the use of long-acting G-CSF (empegfilgrastim) the number of inpatient days could be reduced from 9 to 5.
Conclusion. The results of this study demonstrate the advantage of long-acting G-CSF (empegfilgrastim) as compared with its discrete form (filgrastim) in intensified programs with a reduced inter-cycle interval and high risk of febrile neutropenia (EACODD-14 and EACOРР-14). The use of empegfilgrastim allowed to administer three times as many chemotherapy cycles adhering to the principle of dose intensity in a larger number of patients with advanced cHL stages.
{"title":"Primary Prevention of Neutropenia by Empegfilgrastim in Patients with Advanced Stages of Classical Hodgkin Lymphoma Treated with Intensive First-Line Chemotherapy with a Modified 6-Cycle Program EACODD-14 Under the Protocol “LKh-Rossiya-1”","authors":"Анна Анатольевна Спорник, Н. С. Васильев, А. А. Самойлова, А. А. Мамедова, В. С. Богатырев, Е. Г. Смирнова, А. А. Банникова, А. А. Рукавицын, Н. С. Шорохов, Н. Е. Мочкин, В. О. Саржевский, Е. А. Демина, В. Я. Мельниченко","doi":"10.21320/2500-2139-2023-16-4-370-379","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-370-379","url":null,"abstract":"Aim. To assess the efficacy of a long-acting form of the granulocyte colony-stimulating factor (G-CSF) empegfilgrastim in primary prevention of neutropenia in patients with advanced stages of classical Hodgkin lymphoma (cHL) who received intensive chemotherapy with reduced inter-cycle interval under the protocol “LKh-Rossiya-1”.
 Materials & Methods. The study enrolled 35 patients with newly diagnosed cHL. All patients had advanced stages (IIB X/Е and III/IV) of the disease. They were treated at the NI Pirogov National Medical and Surgical Center from March 2013 to August 2022. The primary prevention of neutropenia by long-acting G-CSF (empegfilgrastim) was administered to 21 patients under the protocol “LKh-Rossiya-1”. They received 6 chemotherapy cycles of modified EACODD-14, in total 126 cycles. The control group consisted of 14 patients who received 6 ЕАСОРР-14 chemotherapy cycles (in total 84 cycles) with dacarbazine as substitution for procarbazine. In the control group, the primary prevention of neutropenia was carried out using discrete G-CSF (filgrastim). The median (range) follow-up in the main (n = 21) and control (n = 14) groups was 18 (5–36) and 39 (29–116) months, respectively. The treatment efficacy was assessed based on PET-CT in 31 patients and on CT in 4 patients.
 Results. By the end of chemotherapy, complete metabolic response was achieved in 28 (80 %) out of 35 patients (95 % in the EACODD-14 and 73 % in ЕАСОРР-14 groups). In 6 (17 %) patients, partial remission was confirmed only by CT scan, and in 1 (3 %) patient, PET/CT showed stabilization. After consolidation radiotherapy, complete remission was reported in all 35 patients. Both groups received the full chemotherapy program per protocol. Without a violation of G-CSF regimen, the EACODD-14 group received 121 (96 %) cycles out of those 126 planned, whereas the ЕАСОРР-14 group received all 84 cycles per protocol. Full implementation of 107 (88.4 %) cycles in the first group and 24 (29 %) cycles in the second group was achieved in 12 (57 %) and 5 (36 %) patients, respectively (p < 0.001). Neutropenia grade 4 was more often identified in filgrastim than in empegfilgrastim recipients (57 % vs. 19 %; p < 0.05) and in a larger number of cycles (15 % vs. 3 %; p < 0.01). The rate of infection episodes in the ЕАСОРР-14 group was higher (50 % vs. 28 %) and in more cycles (15 % vs. 5 %; p < 0.05). Due to the use of long-acting G-CSF (empegfilgrastim) the number of inpatient days could be reduced from 9 to 5.
 Conclusion. The results of this study demonstrate the advantage of long-acting G-CSF (empegfilgrastim) as compared with its discrete form (filgrastim) in intensified programs with a reduced inter-cycle interval and high risk of febrile neutropenia (EACODD-14 and EACOРР-14). The use of empegfilgrastim allowed to administer three times as many chemotherapy cycles adhering to the principle of dose intensity in a larger number of patients with advanced cHL stages.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-387-398
М. М. Канунников, Николай Николаевич Мамаев, Т. Л. Гиндина, А. И. Шакирова, А. М. Садыков, С. В. Разумова, С. Н. Бондаренко, Л. С. Зубаровская
Background. Due to changing views on pathogenesis, risk factors and therapy strategies in prognostically favorable CBF-positive acute myeloid leukemias[1] (AML), the expression monitoring of RUNX1/RUNX1T1 or CBFB/MYH11 fusion genes, as an additional evaluation of treatment outcomes, appears to be insufficient. This indicates the need to improve the monitoring of the CBF+ AML course by means of parallel measurements of BAALC expression levels which roughly correlate with the mass of BAALC-expressing leukemia hematopoietic stem cells (BAALC-e LHSC).
Aim. To improve the quality of assessing treatment outcomes with due account for expression levels of RUNX1/RUNX1T1 or CBFB/MYH11 fusion genes and the mass of BAALC-e LHSC and on this basis to pave the way for personalized CBF+ AML treatment.
Materials & Methods. This study enrolled 39 adult patients aged 20–81 years (median 32 years) and 8 children aged 2–18 years (median 12 years). Among them there were 20 females and 27 males. AML with inv(16)(p13;q22)/t(16;16) was identified in 19 patients, t(8;21)(q22;q22) was detected in 28 patients. BAALC, WT1, RUNX1/RUNX1T1, CBFB/MYH11 expression levels were measured by quantitative real-time PCR and related to the expression of the ABL1 expert gene.
Results. In 23 patients, inv(16) and t(8;21) appeared to be isolated. Additional multidirectional chromosomal changes were observed in 24 patients with inv(16) and in 18 patients with t(8;21). All enrolled patients showed increased BAALC expression. In the course of therapy, it was decreasing to the threshold value in 16/18 (89 %) patients. The evaluation of the mean BAALC expression levels in the pooled groups of children and adults with isolated findings of either inv(16) or t(8;21) showed the decrease of the BAALC-e LHSC mass only in children (p = 0.049). The comparison of the mean WT1 expression levels in the pooled groups of children and adults with isolated and additional chromosomal abnormalities revealed their significant decrease in patients with complicated variants (p = 0.023).
Conclusion. The case reports provided in this paper show that the molecular monitoring with serial measurements of fusion genes and BAALC gene expression levels in CBF+ AML patients can lay the basis for further improvement of personalized treatment strategies for these patients. In all likelihood, parallel measurements of the above gene expression levels will allow to establish the framework for decision-making concerning treatment extent and timely HSC transplantation.
{"title":"BAALC-Expressing Leukemia Hematopoietic Stem Cells and Their Place in the Study of CBF-Positive Acute Myeloid Leukemias in Children and Adults","authors":"М. М. Канунников, Николай Николаевич Мамаев, Т. Л. Гиндина, А. И. Шакирова, А. М. Садыков, С. В. Разумова, С. Н. Бондаренко, Л. С. Зубаровская","doi":"10.21320/2500-2139-2023-16-4-387-398","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-387-398","url":null,"abstract":"Background. Due to changing views on pathogenesis, risk factors and therapy strategies in prognostically favorable CBF-positive acute myeloid leukemias[1] (AML), the expression monitoring of RUNX1/RUNX1T1 or CBFB/MYH11 fusion genes, as an additional evaluation of treatment outcomes, appears to be insufficient. This indicates the need to improve the monitoring of the CBF+ AML course by means of parallel measurements of BAALC expression levels which roughly correlate with the mass of BAALC-expressing leukemia hematopoietic stem cells (BAALC-e LHSC).
 Aim. To improve the quality of assessing treatment outcomes with due account for expression levels of RUNX1/RUNX1T1 or CBFB/MYH11 fusion genes and the mass of BAALC-e LHSC and on this basis to pave the way for personalized CBF+ AML treatment.
 Materials & Methods. This study enrolled 39 adult patients aged 20–81 years (median 32 years) and 8 children aged 2–18 years (median 12 years). Among them there were 20 females and 27 males. AML with inv(16)(p13;q22)/t(16;16) was identified in 19 patients, t(8;21)(q22;q22) was detected in 28 patients. BAALC, WT1, RUNX1/RUNX1T1, CBFB/MYH11 expression levels were measured by quantitative real-time PCR and related to the expression of the ABL1 expert gene.
 Results. In 23 patients, inv(16) and t(8;21) appeared to be isolated. Additional multidirectional chromosomal changes were observed in 24 patients with inv(16) and in 18 patients with t(8;21). All enrolled patients showed increased BAALC expression. In the course of therapy, it was decreasing to the threshold value in 16/18 (89 %) patients. The evaluation of the mean BAALC expression levels in the pooled groups of children and adults with isolated findings of either inv(16) or t(8;21) showed the decrease of the BAALC-e LHSC mass only in children (p = 0.049). The comparison of the mean WT1 expression levels in the pooled groups of children and adults with isolated and additional chromosomal abnormalities revealed their significant decrease in patients with complicated variants (p = 0.023).
 Conclusion. The case reports provided in this paper show that the molecular monitoring with serial measurements of fusion genes and BAALC gene expression levels in CBF+ AML patients can lay the basis for further improvement of personalized treatment strategies for these patients. In all likelihood, parallel measurements of the above gene expression levels will allow to establish the framework for decision-making concerning treatment extent and timely HSC transplantation.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-02DOI: 10.21320/2500-2139-2023-16-4-361-369
Екатерина Сергеевна Нестерова, E. E. Звонков, А. М. Ковригина, Т. Н. Обухова, Б. В. Бидерман, А. Б. Судариков, Я. К. Мангасарова, А. У. Магомедова, А. К. Смольянинова, С. М. Куликов, Е. Н. Паровичникова
Aim. To determine the prognostic value of t(14;18)(q32;q21) in follicular lymphoma (FL) of grades 1–3А, to assess the chemotherapy efficacy in “t(14;18)+ FL” and “t(14;18)– FL” patients, and to analyze the cases of ineffective therapy.
Materials & Methods. The retrospective/prospective study carried out at the National Research Center for Hematology in the period of 2001–2022 enrolled 362 patients with newly diagnosed FL of grades 1–3А. Their risk stratification was based on predictive models FLIPI and PPI3 (Personalized Predictive Index[1]). The patients were 30–81 years of age (median 52 years). There were 225 women and 137 men. They received the following regimens: R-B (n = 80), R-CHOP (n = 189), R-CHOP (4 cycles) + R-DHAP (2 cycles) (n = 28), and R-CHOP (4 cycles) + R-DHAP (2 cycles) + auto-HSCT in the first-line therapy (n = 65). For 2 years, maintenance rituximab therapy was administered to all the enrolled patients, whichever drug chemotherapy they received. Standard cytogenetic analysis and FISH were carried out in 265/362 (73 %) patients.
Results. Patients were divided into two comparable groups: “t(14;18)+ FL” (n = 196) and “t(14;18)– FL” (n = 69). Patients without cytogenetics/FISH (n = 97) were excluded from the analysis. In patients without t(14;18), poor prognostic factors, such as grade 3А (p = 0.003) and Ki-67 > 35 % (p = 0.001), were identified significantly more often, and also high PPI3 risk was reported (p = 0.008). No differences (p = 0.84) were detected during FLIPI risk stratification of patients. Bone marrow lesions were observed significantly more often in “t(14;18)+ FL” compared to “t(14;18)– FL” (p = 0.002). The chemotherapy outcomes, such as 2-year EFS and OS, appeared to be considerably worse in “t(14;18)– FL” compared to “t(14;18)+ FL” patients.
Conclusion. The group of FL patients with t(14;18) appeared to be most numerous and more prognostically favorable. Immunochemotherapy regimens R-B and R-CHOP are more justified in the first-line therapy of FL with low PPI3 risk. Therapy outcomes were comparable in efficacy. In intermediate and high PPI3 risk FL patients with t(14;18), the most effective first-line therapy was the one with consistent administration of R-CHOP, R-DHAP, and auto-HSCT. Based on the results of this study, FL of grades 1–3А without t(14;18) can well be considered to be a prognostically unfavorable variant of this malignant lymphoid tumor. The rate of early relapses/progression after the standard immunochemotherapy (R-B and R-CHOP), according to our data, is 60 %. In patients with newly diagnosed FL who received consistent administration of R-CHOP, R-DHAP, and auto-HSCT in the first-line therapy, this rate drops to 30 %. Our results clearly indicate the need for new FL treatment approaches.
{"title":"Фолликулярная лимфома 1–3А цитологического типа с наличием или отсутствием t(14;18)(q32;q21): прогноз, выбор противоопухолевой терапии и ее результаты","authors":"Екатерина Сергеевна Нестерова, E. E. Звонков, А. М. Ковригина, Т. Н. Обухова, Б. В. Бидерман, А. Б. Судариков, Я. К. Мангасарова, А. У. Магомедова, А. К. Смольянинова, С. М. Куликов, Е. Н. Паровичникова","doi":"10.21320/2500-2139-2023-16-4-361-369","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-4-361-369","url":null,"abstract":"Aim. To determine the prognostic value of t(14;18)(q32;q21) in follicular lymphoma (FL) of grades 1–3А, to assess the chemotherapy efficacy in “t(14;18)+ FL” and “t(14;18)– FL” patients, and to analyze the cases of ineffective therapy.
 Materials & Methods. The retrospective/prospective study carried out at the National Research Center for Hematology in the period of 2001–2022 enrolled 362 patients with newly diagnosed FL of grades 1–3А. Their risk stratification was based on predictive models FLIPI and PPI3 (Personalized Predictive Index[1]). The patients were 30–81 years of age (median 52 years). There were 225 women and 137 men. They received the following regimens: R-B (n = 80), R-CHOP (n = 189), R-CHOP (4 cycles) + R-DHAP (2 cycles) (n = 28), and R-CHOP (4 cycles) + R-DHAP (2 cycles) + auto-HSCT in the first-line therapy (n = 65). For 2 years, maintenance rituximab therapy was administered to all the enrolled patients, whichever drug chemotherapy they received. Standard cytogenetic analysis and FISH were carried out in 265/362 (73 %) patients.
 Results. Patients were divided into two comparable groups: “t(14;18)+ FL” (n = 196) and “t(14;18)– FL” (n = 69). Patients without cytogenetics/FISH (n = 97) were excluded from the analysis. In patients without t(14;18), poor prognostic factors, such as grade 3А (p = 0.003) and Ki-67 > 35 % (p = 0.001), were identified significantly more often, and also high PPI3 risk was reported (p = 0.008). No differences (p = 0.84) were detected during FLIPI risk stratification of patients. Bone marrow lesions were observed significantly more often in “t(14;18)+ FL” compared to “t(14;18)– FL” (p = 0.002). The chemotherapy outcomes, such as 2-year EFS and OS, appeared to be considerably worse in “t(14;18)– FL” compared to “t(14;18)+ FL” patients.
 Conclusion. The group of FL patients with t(14;18) appeared to be most numerous and more prognostically favorable. Immunochemotherapy regimens R-B and R-CHOP are more justified in the first-line therapy of FL with low PPI3 risk. Therapy outcomes were comparable in efficacy. In intermediate and high PPI3 risk FL patients with t(14;18), the most effective first-line therapy was the one with consistent administration of R-CHOP, R-DHAP, and auto-HSCT. Based on the results of this study, FL of grades 1–3А without t(14;18) can well be considered to be a prognostically unfavorable variant of this malignant lymphoid tumor. The rate of early relapses/progression after the standard immunochemotherapy (R-B and R-CHOP), according to our data, is 60 %. In patients with newly diagnosed FL who received consistent administration of R-CHOP, R-DHAP, and auto-HSCT in the first-line therapy, this rate drops to 30 %. Our results clearly indicate the need for new FL treatment approaches.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134969004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-09DOI: 10.21320/2500-2139-2023-16-3-229-241
Сергей Вячеславович Семочкин
In recent decades, the progress in multiple myeloma (MM) treatment has been linked to a clearer insight into the biology of this disease and practical application of new pharmaceutical classes, such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (MABs). Modern IMiDs (lenalidomide and pomalidomide) are thalidomide derivatives which despite the similarity of chemical structure show only a relative cross-resistance. Lenalidomide is a second-generation immunomodulator with high anti-tumor activity and a favorable safety profile. In 2006, the use of lenalidomide combined with dexamethasone (Rd regimen) was approved by FDA (USA) for the treatment of relapsed/refractory MM, and 9 years later, in 2015, for newly diagnosed MM. During 2015–2019, the treatment of relapsed MM applied the newly developed regimens involving Rd combined with bortezomib (VRd), carfilzomib (KRd), ixazomib (IRd), elotuzumab (ERd), and daratumumab (DRd), the so-called triplets. Pomalidomide is a third-generation drug used in lenalidomide-refractory patients. For patients with relapsed/refractory MM who received at least two therapy lines with lenalidomide and bortezomib, regimens with 3 drugs were introduced which include pomalidomide and dexamethasone combined with elotuzumab (EPd), isatuximab (Isa-Pd), and daratumumab (DPd). In 2010, the molecular target of IMiD action was discovered, that is protein cereblon (CRBN), a component of CRBN E3 ligase enzyme complex. The insight into this mechanism provided the basis for developing a new family of thalidomide derivatives which are now called CRBN E3 ligase modulators (CELMoDs). In phase I/II trials, two drugs belonging to this group (iberdomide and mezigdomide) showed promising activity in MM refractory to three classes of antitumor drugs (IMiDs, PIs, and anti-CD38 MABs). The present review is focused on prospective studies of IMiDs and CELMoDs at different stages of MM treatment.
{"title":"Перспективы применения иммуномодулирующих препаратов и модуляторов цереблон Е3-лигазы в лечении множественной миеломы","authors":"Сергей Вячеславович Семочкин","doi":"10.21320/2500-2139-2023-16-3-229-241","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-3-229-241","url":null,"abstract":"In recent decades, the progress in multiple myeloma (MM) treatment has been linked to a clearer insight into the biology of this disease and practical application of new pharmaceutical classes, such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (MABs). Modern IMiDs (lenalidomide and pomalidomide) are thalidomide derivatives which despite the similarity of chemical structure show only a relative cross-resistance. Lenalidomide is a second-generation immunomodulator with high anti-tumor activity and a favorable safety profile. In 2006, the use of lenalidomide combined with dexamethasone (Rd regimen) was approved by FDA (USA) for the treatment of relapsed/refractory MM, and 9 years later, in 2015, for newly diagnosed MM. During 2015–2019, the treatment of relapsed MM applied the newly developed regimens involving Rd combined with bortezomib (VRd), carfilzomib (KRd), ixazomib (IRd), elotuzumab (ERd), and daratumumab (DRd), the so-called triplets. Pomalidomide is a third-generation drug used in lenalidomide-refractory patients. For patients with relapsed/refractory MM who received at least two therapy lines with lenalidomide and bortezomib, regimens with 3 drugs were introduced which include pomalidomide and dexamethasone combined with elotuzumab (EPd), isatuximab (Isa-Pd), and daratumumab (DPd). In 2010, the molecular target of IMiD action was discovered, that is protein cereblon (CRBN), a component of CRBN E3 ligase enzyme complex. The insight into this mechanism provided the basis for developing a new family of thalidomide derivatives which are now called CRBN E3 ligase modulators (CELMoDs). In phase I/II trials, two drugs belonging to this group (iberdomide and mezigdomide) showed promising activity in MM refractory to three classes of antitumor drugs (IMiDs, PIs, and anti-CD38 MABs). The present review is focused on prospective studies of IMiDs and CELMoDs at different stages of MM treatment.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135215072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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