Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group
The course of multiple myeloma (MM) is influenced by a variety of factors, including the specificity of the tumour microenvironment (TME). The aim of this review is to provide insight into the interplay of treatment modalities used in the current clinical practice and TME. Bortezomib-based triplets...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/17/3940 |
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| author | Jelena Bila Eirini Katodritou Margarita Guenova Sandra Basic-Kinda Daniel Coriu Milena Dapcevic Lejla Ibricevic-Balic Arben Ivanaj Oliver Karanfilski Samo Zver Meral Beksac Evangelos Terpos Meletios Athanassios Dimopoulos |
| author_facet | Jelena Bila Eirini Katodritou Margarita Guenova Sandra Basic-Kinda Daniel Coriu Milena Dapcevic Lejla Ibricevic-Balic Arben Ivanaj Oliver Karanfilski Samo Zver Meral Beksac Evangelos Terpos Meletios Athanassios Dimopoulos |
| author_sort | Jelena Bila |
| collection | DOAJ |
| description | The course of multiple myeloma (MM) is influenced by a variety of factors, including the specificity of the tumour microenvironment (TME). The aim of this review is to provide insight into the interplay of treatment modalities used in the current clinical practice and TME. Bortezomib-based triplets are the standard for MM first-line treatment. Bortezomib is a proteasome inhibitor (PI) which inhibits the nuclear factor kappa B (NF-κB) pathway. However, bortezomib is decreasing the expression of chemokine receptor CXCR4 as well, possibly leading to the escape of extramedullary disease. Immunomodulatory drugs (IMiDs), lenalidomide, and pomalidomide downregulate regulatory T cells (Tregs). Daratumumab, anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody (MoAb), downregulates Tregs CD38+. Bisphosphonates inhibit osteoclasts and angiogenesis. Sustained suppression of bone resorption characterises the activity of MoAb denosumab. The plerixafor, used in the process of stem cell mobilisation and harvesting, block the interaction of chemokine receptors CXCR4-CXCL12, leading to disruption of MM cells’ interaction with the TME, and mobilisation into the circulation. The introduction of several T-cell-based immunotherapeutic modalities, such as chimeric-antigen-receptor-transduced T cells (CAR T cells) and bispecific antibodies, represents a new perspective in MM treatment affecting TME immune evasion. The optimal treatment approach to MM patients should be adjusted to all aspects of the individual profile including the TME niche. |
| first_indexed | 2024-03-10T08:08:47Z |
| format | Article |
| id | doaj.art-6912ec691bf643e197e4b1f6b2cdf84b |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T08:08:47Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-6912ec691bf643e197e4b1f6b2cdf84b2023-11-22T10:49:41ZengMDPI AGJournal of Clinical Medicine2077-03832021-08-011017394010.3390/jcm10173940Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study GroupJelena Bila0Eirini Katodritou1Margarita Guenova2Sandra Basic-Kinda3Daniel Coriu4Milena Dapcevic5Lejla Ibricevic-Balic6Arben Ivanaj7Oliver Karanfilski8Samo Zver9Meral Beksac10Evangelos Terpos11Meletios Athanassios Dimopoulos12Clinic of Hematology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Hematology, Theagenio Cancer Hospital, 54639 Thessaloniki, GreeceLaboratory of Haematopathology and Immunology, National Specialised Hospital for Active Treatment of Haematological Diseases, 1756 Sofia, BulgariaDivison of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaCentre of Hematology and Bone Marrow Transplant, “Fundeni” Clinical Institute, “Carol Davila” University of Medicine and Pharmacy, 022328 Bucharest, RomaniaDivision of Hematology, Clinical Center of Montenegro, Podgorica 81000, MontenegroClinic of Hematology, University Clinical Center of Sarajevo, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Hematology, University Medical Center “Mother Teresa”, 1001 Tirana, AlbaniaUniversity Clinic of Hematology, Faculty of Medicine, University of Skopje, 1000 Skopje, North MacedoniaDepartment of Hematology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaDepartment of Hematology, Tissue Typing Laboratory and Donor Registry, Faculty of Medicine, University of Ankara, Ankara 06590, TurkeyDepartment of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceThe course of multiple myeloma (MM) is influenced by a variety of factors, including the specificity of the tumour microenvironment (TME). The aim of this review is to provide insight into the interplay of treatment modalities used in the current clinical practice and TME. Bortezomib-based triplets are the standard for MM first-line treatment. Bortezomib is a proteasome inhibitor (PI) which inhibits the nuclear factor kappa B (NF-κB) pathway. However, bortezomib is decreasing the expression of chemokine receptor CXCR4 as well, possibly leading to the escape of extramedullary disease. Immunomodulatory drugs (IMiDs), lenalidomide, and pomalidomide downregulate regulatory T cells (Tregs). Daratumumab, anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody (MoAb), downregulates Tregs CD38+. Bisphosphonates inhibit osteoclasts and angiogenesis. Sustained suppression of bone resorption characterises the activity of MoAb denosumab. The plerixafor, used in the process of stem cell mobilisation and harvesting, block the interaction of chemokine receptors CXCR4-CXCL12, leading to disruption of MM cells’ interaction with the TME, and mobilisation into the circulation. The introduction of several T-cell-based immunotherapeutic modalities, such as chimeric-antigen-receptor-transduced T cells (CAR T cells) and bispecific antibodies, represents a new perspective in MM treatment affecting TME immune evasion. The optimal treatment approach to MM patients should be adjusted to all aspects of the individual profile including the TME niche.https://www.mdpi.com/2077-0383/10/17/3940multiple myelomabone marrow microenvironmenttreatment |
| spellingShingle | Jelena Bila Eirini Katodritou Margarita Guenova Sandra Basic-Kinda Daniel Coriu Milena Dapcevic Lejla Ibricevic-Balic Arben Ivanaj Oliver Karanfilski Samo Zver Meral Beksac Evangelos Terpos Meletios Athanassios Dimopoulos Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group Journal of Clinical Medicine multiple myeloma bone marrow microenvironment treatment |
| title | Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group |
| title_full | Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group |
| title_fullStr | Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group |
| title_full_unstemmed | Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group |
| title_short | Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group |
| title_sort | bone marrow microenvironment interplay and current clinical practice in multiple myeloma a review of the balkan myeloma study group |
| topic | multiple myeloma bone marrow microenvironment treatment |
| url | https://www.mdpi.com/2077-0383/10/17/3940 |
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