Monoclonal and Bispecific Anti-BCMA Antibodies in Multiple Myeloma
Abstract
:1. Introduction
2. Biologic Role of BCMA in MM Cells
3. BCMA as a Therapeutic Target
4. Investigational Antibody-Based Approach Targeting BCMA
4.1. Antibody-Drug Conjugate: Mechanism and Preclinical Model
4.1.1. Clinical Trials, Patient Population and Efficacy
4.1.2. Toxicity
4.2. Bispecific Antibodies
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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TRIAL NAME | NCT Number | PHASE | Number of Patients (Treatment Arm) | Previous Lines of Treatment (Median) | Previous Drugs | Combinatio n with Other Drugs | Efficacy | Aes (Grade 3–4) | Reference |
---|---|---|---|---|---|---|---|---|---|
BMA117159 | NCT02064387 | I | 35 (part 2) | 1–≥10 | IMIDs PIs Alkilators | / | ORR 60% Median PFS 12 Months | Corneal Events (9%), Thrombocytopenia (26%), Anaemia (14%) | Trudel S, Blood Cancer Journal (2019) 9:37 |
DREAMM-2 | NCT03525678 | II | 196 | 3–21 (7) | IMIDs PIs Anti-CD38 | / | ORR: 31% (2.5 mg/kg), 34% (3.4 mg/kg)Median PFS: 2.8 (2.5 mg/kg), 3.9 Months (3.4 mg/kg) | Kerathopathy (27% and 21%) Thrombocytopenia (20% and 33%) Anemia (20% And 25%) | Lonial S, Lancet Oncol 2020; 21:207–221 |
DREAMM-4 | NCT03848845 | I/II | 13 (part 1) | 3–13 (7.5)–2.5 mg/kg cohort 3–8 (5)–3.4 mg/kg cohort | IMIDs PIs Anti-CD38 | Pembrolizumab | ORR: 67% (2.5 mg/kg Cohort), 14% (3.4 mg/kg Cohort) | Kerathopathy (33% and 57%) | Nooka AJ, EHA2020, Abs EP955 |
DRUG NAME | TRIAL NAME | NCT Number | PHASE | Setting | Combination with Other Drugs | Comparator Arm |
---|---|---|---|---|---|---|
GSK2857916 | BMA117159 | NCT02064387 | I | RRMM | / | / |
DREAMM-2 | NCT03525678 | II | RRMM | / | / | |
DREAMM-3 | NCT04162210 | III | RRMM | / | Pomalidomide/Dexamethasone | |
DREAMM-4 | NCT03848845 | I/II | RRMM | Pembrolizumab | / | |
DREAMM-5 | NCT04126200 | I/II | RRMM | GSK3174998 GSK3359609 Nirogacestat | / | |
DREAMM-6 | NCT03544281 | I/II | RRMM | Lenalidomide/Dexamethasone Bortezomib/Dexamethasone | / | |
DREAMM-7 | NCT04246047 | III | RRMM | Bortezomib/Dexamethasone | Daratumumab/Bortezomib/Dexamethasone | |
DREAMM-8 | NCT04484623 | III | RRMM | Pomalidomide/Dexamethasone | Pomalidomide/Bortezomib/dexamethasone | |
MCRN 007 | NCT03715478 | I/II | RRMM | Pomalidomide/Dexamethasone | / | |
209664 | NCT04091126 | I | NDMM | Bortezomib/Lenalidomide/Dexamethasone | / | |
MEDI2228 | D7900C00001 | NCT03489525 | I | RRMM | / | / |
CC99712 | CC-99712-MM-001 | NCT04036461 | I | RRMM | / | / |
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Dalla Palma, B.; Marchica, V.; Catarozzo, M.T.; Giuliani, N.; Accardi, F. Monoclonal and Bispecific Anti-BCMA Antibodies in Multiple Myeloma. J. Clin. Med. 2020, 9, 3022. https://doi.org/10.3390/jcm9093022
Dalla Palma B, Marchica V, Catarozzo MT, Giuliani N, Accardi F. Monoclonal and Bispecific Anti-BCMA Antibodies in Multiple Myeloma. Journal of Clinical Medicine. 2020; 9(9):3022. https://doi.org/10.3390/jcm9093022
Chicago/Turabian StyleDalla Palma, Benedetta, Valentina Marchica, Maria Teresa Catarozzo, Nicola Giuliani, and Fabrizio Accardi. 2020. "Monoclonal and Bispecific Anti-BCMA Antibodies in Multiple Myeloma" Journal of Clinical Medicine 9, no. 9: 3022. https://doi.org/10.3390/jcm9093022