Past, Present, and a Glance into the Future of Multiple Myeloma Treatment
Abstract
:1. The Pathogenesis of Multiple Myeloma
2. The Existing Therapies for MM
2.1. Mechanism of Action of Proteasome Inhibitors
2.2. Mechanism of Action of Immunomodulatory Drugs
2.3. Mechanism of Action of Histone Deacetylase Inhibitors
3. The Development of Immunotherapies in MM
3.1. Monoclonal Antibodies
3.2. Antibody–Drug Conjugate
3.3. Bispecific Antibodies
3.4. Chimeric Antigen Receptor-Modified T-Cells and NK Cells
4. Glance into the Future
4.1. Targeting the Apoptotic Pathway in MM
Bcl-2 Family Inhibitors
4.2. Targeting MM Cancer Stem Cells
4.3. Targeting the Bone Marrow Microenvironment
Bruton’s Tyrosine Kinase Inhibitors
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drug | Year | Treatment | Adverse Effects | Refs. |
---|---|---|---|---|
Thalidomide | 2006 | NDMM | somnolence, constipation, neuropathy, VTE, and rash | [48,49] |
Lenalidomide | 2006 | Received one prior therapy | neutropenia, thrombocytopenia, leukopenia, lymphopenia, febrile neutropenia, deep vein thrombosis, pulmonary embolism, atrial fibrillation, constipation, diarrhea, fatigue, pneumonia, hypokalemia, hypocalcemia, muscle weakness, neuropathy, and depression | [50] |
Doxorubicin | 2007 | RRMM | thrombocytopenia, neutropenia, anemia, fatigue, pyrexia, nausea, vomiting, mucositis/stomatitis diarrhea, and hand foot syndrome | [49,51] |
Bortezomib | 2008 | NDMM | asthenic conditions, diarrhea, constipation, PSN, vomiting, nausea psychiatric disorders, pyrexia, anorexia, thrombocytopenia, leukopenia, neuralgia, neutropenia, and anemia | [49,52] |
Plerixafor | 2008 | MM | diarrhea, vomiting, nausea, fatigue, headache, injection site reactions, dizziness, and arthralgia | [49,53] |
Carfilzomib | 2012 | RRMM | fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, pyrexia, pneumonia, ARF, pyrexia, and CHF | [54] |
Pomalidomide | 2013 | RRMM | asthenia, fatigue, neutropenia, anemia, constipation, diarrhea, nausea, URTI, dyspnea, back pain, and pyrexia | [55] |
Drug | Year | Treatment | Adverse Effects | Name and NCT Number | Refs. |
---|---|---|---|---|---|
Panobinostat | 2015 | RRMM | pneumonia, diarrhea, arrhythmias, hypophosphatemia and hypokalemia, ECG change, thrombocytopenia, neutropenia fatigue, and sepsis | PANORAMA1 NCT01023308 | [69] |
Carfilzomib | 2015 | RRMM | CVE, VTE, ARF, pulmonary toxicities, hypertension, and thrombocytopenia | ASPIRE NCT01080391 | [70] |
Daratumumab | 2015 | RRMM | fatigue, nausea, back pain, pyrexia, URTI, cough, IRs, lymphopenia, neutropenia, anemia, and thrombocytopenia | SIRIUS NCT01985126 | [71] |
Ixazomib | 2015 | RRMM | diarrhea, constipation, thrombocytopenia, PSN, nausea, peripheral edema, vomiting, and back pain | TOURMALITOURMALINE NCT01564537 | [47] |
Elotuzumab | 2015 | RRMM | ARF, pneumonia, nasopharyngitis pyrexia, anemia, pulmonary embolism, and PSN | ELOQUENT-2 NCT01239797 | [72] [73] |
Daratumumab | 2016 | RRMM | URTI, cough, diarrhea, fatigue, nausea, pyrexia, muscle spasm, and dyspnea, neutropenia, anemia | POLLUX NCT02076009 | [74] |
Daratumumab | 2016 | RRMM | URTI, IRs, diarrhea, peripheral edema, Neutropenia, and thrombocytopenia, anemia | CASTOR NCT02136134 | [75,76] |
Daratumumab | 2019 | NTE NDMM | IRs, URTI, diarrhea, constipation, peripheral edema, nausea, fatigue, asthenia, dyspnea, pyrexia, muscle spasms, and PSN | MAIA NTC02252172 | [66,77,78] |
Selinexor | 2019 | RRMM | Thrombocytopenia, fatigue, nausea, anemia, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and URTI | STORM KCP-330-012 NCT02336815 | [79,80] |
Daratumumab | 2019 | TE NDMM | IRs, PSN, constipation, asthenia, nausea, neutropenia, thrombocytopenia, peripheral edema, pyrexia and paresthesia | CASSIOPEIA NCT02541383 | [81] |
Drug | Year | Treatment | Adverse Effects | Name & NCT Number | Refs. |
---|---|---|---|---|---|
Isatuximab | 2020 | RRMM | neutropenia, IRs, pneumonia, URTI, and diarrhea | ICARIA-MM NCT02990338 | [62] |
Daratumumab | 2020 | RRMM | URTI, constipation, nausea, fatigue, pyrexia, PSN, diarrhea, cough, insomnia, vomiting, back pain, muscle spasms, dyspnea, neutropenia, thrombocytopenia, and anemia | COLUMBA NCT03277105 | [129] |
Belantamab mafodotin | 2020 | RRMM | keratopathy, decreased visual acuity, nausea, blurred vision, pyrexia, IRs, and fatigue | DREAMM-2 NCT 03525678 | [130,131] |
Carfilzomib | 2020 | RRMM | IRs, anemia, diarrhea, fatigue, hypertension, pyrexia, respiratory tract infection, thrombocytopenia, anemia, neutropenia, lymphopenia, cough, dyspnea, insomnia, hypertension, headache, and back pain | EQUULEUS NCT01998971CANDOR NCT03158688 | [132] |
Selinexor | 2020 | RRMM | Nausea, fatigue, decreased appetite, diarrhea, PSN, URTI, decreased weight, cataract, vomiting, thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia, and neutropenia. | BOSTON NCT03110562 | [78,133] |
Melphalan flufenamide | 2021 | RRMM | fatigue, nausea, diarrhea, pyrexia, neutropenia, thrombocytopenia, anemia, and pneumonia | HORIZON NCT02963493 | [134] |
Idecabtagene vicleucel | 2021 | RRMM | CRS, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, prolonged cytopenias, infections, fatigue, musculoskeletal pain, and hypogammaglobulinemia. | KarMMa NCT02658929 | [135] |
Isatuximab | 2021 | NTE NDMM | URTI, bronchitis, cough, diarrhea, IRs, fatigue, hypertension, thrombocytopenia, and anemia | IKEMA NCT03275285 | [82,136] |
Daratumumab | 2021 | RRMM | IRs, fatigue, pneumonia, upper respiratory tract infection, and diarrhea, neutropenia, thrombocytopenia, anemia, and hyperglycemia | APOLLO NCT03180736 | [137] |
Daratumumab | 2021 | RRMM | URTI, hypertension, diarrhea, cough, fatigue, insomnia, pyrexia, nausea, and peripheral edema | PLEIADES NCT03412565 | [138] |
Ciltacabtagene autoleucel | 2022 | RRMM | pyrexia, cytokine release syndrome, hypogammaglobulinemia, musculoskeletal pain, fatigue, infections, diarrhea, nausea, encephalopathy, headache, coagulopathy, constipation, and vomiting | CARTITUDE-1 NCT03548207 | [139] |
Teclistamab-cqyv | 2022 | RRMM | CRS, ICANS, fatigue, pneumonia, diarrhea, pyrexia, neutropenia, thrombocytopenia, and anemia | MajesTEC-1 NCT0314518, NCT04557098 | [140,141] |
Name/Target | Combination | Patients’ Status | Trial Number | Phase | Recruiting Status |
---|---|---|---|---|---|
Anti-BCMA/GPRC5D | RRMM | NCT05509530 | Phase II | Recruiting | |
APRIL CAR-T cells | BCMA/TACI Positive RRMM | NCT04657861 | Early Phase I | Recruiting | |
Dual Specificity CD38 and BCMA | RRMM | NCT03767751 | Phase I | Unknown | |
Anti-BCMA | Fludarabine Cyclophosphamide | MM | NCT03322735 | Phase I | Unknown |
SLAMF7 CAR-T | MM | NCT04499339 | Phase I/IIa | Recruiting | |
CXCR4 modified anti-BCMA CAR T-cells | MM | NCT04727008 | Early Phase I | Not yet recruiting | |
CD19-CD22 CAR-T-cells | RRMM | NCT04714827 | Phase I/II | Recruiting | |
BCMA/CD19 Dual-Target CAR-T | RRMM | NCT04182581 | Early Phase I | Unknown | |
CD 70 CAR T | CD70 Positive RRMM | NCT04662294 | Early Phase I | Recruiting | |
Anti-CD38 CAR-T | RRMM | NCT03464916 | Phase I | Completed | |
Bispecific CAR Targeting CS1 and BCMA | RRMM | NCT03464916 | Phase I | Completed | |
Anti-BCMA | clarithromycin, lenalidomide, dexamethasone | NDMM | NCT04287660 | Phase III | Recruiting |
Anti-BCMA CAR-NK | RRMM | NCT03940833 | Phase I/II | Unknown | |
Anti-BCMA CAR-NK | Fludarabine Cytoxan | RRMM | NCT05008536 | Early Phase I | Recruiting |
Anti-BCMA CAR-NK | Cyclophosphamide Fludarabine Daratumumab | MM | NCT05182073 | Phase I | Recruiting |
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Elbezanti, W.O.; Challagundla, K.B.; Jonnalagadda, S.C.; Budak-Alpdogan, T.; Pandey, M.K. Past, Present, and a Glance into the Future of Multiple Myeloma Treatment. Pharmaceuticals 2023, 16, 415. https://doi.org/10.3390/ph16030415
Elbezanti WO, Challagundla KB, Jonnalagadda SC, Budak-Alpdogan T, Pandey MK. Past, Present, and a Glance into the Future of Multiple Myeloma Treatment. Pharmaceuticals. 2023; 16(3):415. https://doi.org/10.3390/ph16030415
Chicago/Turabian StyleElbezanti, Weam Othman, Kishore B. Challagundla, Subash C. Jonnalagadda, Tulin Budak-Alpdogan, and Manoj K. Pandey. 2023. "Past, Present, and a Glance into the Future of Multiple Myeloma Treatment" Pharmaceuticals 16, no. 3: 415. https://doi.org/10.3390/ph16030415