Belantamab Mafodotin to Treat Multiple Myeloma: A Comprehensive Review of Disease, Drug Efficacy and Side Effects

Grace Lassiter, Cole Bergeron, Ryan Guedry, Julia Cucarola, Adam M Kaye, Elyse M Cornett, Alan D Kaye, Giustino Varrassi, Omar Viswanath, Ivan Urits, Grace Lassiter, Cole Bergeron, Ryan Guedry, Julia Cucarola, Adam M Kaye, Elyse M Cornett, Alan D Kaye, Giustino Varrassi, Omar Viswanath, Ivan Urits

Abstract

Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed.

Keywords: anti-B cell maturation antigen; antibody drug conjugate; belantamab mafodotin; chronic pain; multiple myeloma.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Bird S., Boyd K. Multiple myeloma: An overview of management. Palliat. Care Soc. Pract. 2019;13 doi: 10.1177/1178224219868235.
    1. Albagoush S.A., Azevedo A.M. Multiple Myeloma. StatPearls Publishing; Treasure Island, FL, USA: 2020. [(accessed on 13 July 2020)]. Available online:
    1. Michels T.C., Petersen K.E. Multiple Myeloma: Diagnosis and Treatment. Am. Fam. Physician. 2017;95:373–383.
    1. Cowan A.J., Allen C., Barac A., Basaleem H., Bensenor I., Curado M.P., Foreman K., Gupta R., Harvey J., Hosgood H.D., et al. Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018;4:1221–1227. doi: 10.1001/jamaoncol.2018.2128.
    1. Howlader N., Noone A.M., Krapcho M., Miller D., Bishop K., Kosary C.L. Myeloma—Cancer Stat Facts [Internet]. SEER Cancer Statistics Review, 1975–2014. [(accessed on 10 December 2020)];2017 Available online: .
    1. Kumar S.K., Rajkumar S.V., Dispenzieri A., Lacy M.Q., Hayman S.R., Buadi F.K., Zeldenrust S.R., Dingli D., Russell S.J., Lust J.A., et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–2520. doi: 10.1182/blood-2007-10-116129.
    1. Trudel S., Lendvai N., Popat R., Voorhees P.M., Reeves B., Libby E.N., Richardson P.G., Hoos A., Gupta I., Bragulat V., et al. Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: An update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019;9:1–10. doi: 10.1038/s41408-019-0196-6.
    1. Teras L.R., DeSantis C.E., Cerhan J.R., Morton L.M., Jemal A., Flowers C.R. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA A Cancer J. Clin. 2016;66:443–459. doi: 10.3322/caac.21357.
    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA A Cancer J. Clin. 2020;70:7–30. doi: 10.3322/caac.21590.
    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2016. CA A Cancer J. Clin. 2016;66:7–30. doi: 10.3322/caac.21332.
    1. Castaneda O., Baz R. Multiple Myeloma Genomics—A Concise Review. Acta Med. Acad. 2019;48:57–67.
    1. Kuehl W.M., Bergsagel P.L. Molecular pathogenesis of multiple myeloma and its premalignant precursor. J. Clin. Investig. 2012;122:3456–3463. doi: 10.1172/JCI61188.
    1. Pawlyn C., Davies F.E. Toward personalized treatment in multiple myeloma based on molecular characteristics. Blood. 2019;133:660–675. doi: 10.1182/blood-2018-09-825331.
    1. Brioli A., Melchor L., Cavo M., Morgan G.J. The impact of intra-clonal heterogeneity on the treatment of multiple myeloma. Br. J. Haematol. 2014;165:441–454. doi: 10.1111/bjh.12805.
    1. Rajkumar V.S. Multiple myeloma: Every year a new standard? Hematol. Oncol. 2019;37:62–65. doi: 10.1002/hon.2586.
    1. Kyle R.A., Gertz M.A., Witzig T.E., Lust J.A., Lacy M.Q., Dispenzieri A., Fonseca R., Rajkumar S.V., Offord J.R., Larson D.R., et al. Review of 1027 Patients With Newly Diagnosed Multiple Myeloma. Mayo Clin. Proc. 2003;78:21–33. doi: 10.4065/78.1.21.
    1. Eslick R., Talaulikar D. Multiple myeloma: From diagnosis to treatment. Aust. Fam. Physician. 2013;42:684–688.
    1. Diercks D.B., Shumaik G.M., Harrigan R.A., Brady W.J., Chan T.C. Electrocardiographic manifestations: Electrolyte abnormalities. J. Emerg. Med. 2004;27:153–160. doi: 10.1016/j.jemermed.2004.04.006.
    1. Rajkumar V.S., Kumar S.K. Multiple Myeloma: Diagnosis and Treatment. Mayo Clin. Proc. 2016;91:101–119. doi: 10.1016/j.mayocp.2015.11.007.
    1. Kristinsson S.Y., Minter A.R., Korde N., Tan E., Landgren O. Bone disease in multiple myeloma and precursor disease: Novel diagnostic approaches and implications on clinical management. Expert Rev. Mol. Diagn. 2011;11:593–603. doi: 10.1586/erm.11.44.
    1. Abramson H.N. B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma. Int. J. Mol. Sci. 2020;21:5192. doi: 10.3390/ijms21155192.
    1. Mogollón P., Díaz-Tejedor A., Algarín E.M., Paíno T., Garayoa M., Ocio E.M. Biological Background of Resistance to Current Standards of Care in Multiple Myeloma. Cells. 2019;8:1432. doi: 10.3390/cells8111432.
    1. Rajkumar V.S. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am. J. Hematol. 2020;95:548–567. doi: 10.1002/ajh.25791.
    1. Rajkumar S.V., Rajkumar V., Kyle R.A., Van Duin M., Sonneveld P., Mateos M.-V., Gay F., Anderson K.C. Multiple myeloma. Nat. Rev. Dis. Prim. 2017;3:17046. doi: 10.1016/j.currproblcancer.2009.01.001.
    1. Shah N., Chari A., Scott E., Mezzi K., Usmani S.Z. B-cell maturation antigen (BCMA) in multiple myeloma: Rationale for targeting and current therapeutic approaches. Leukemia. 2020;34:985–1005. doi: 10.1038/s41375-020-0734-z.
    1. D’Agostino M., Raje N.S. Anti-BCMA CAR T-cell therapy in multiple myeloma: Can we do better? Leukemia. 2019;34:21–34. doi: 10.1038/s41375-019-0669-4.
    1. Bazarbachi A.H., Al Hamed R., Malard F., Harousseau J.-L., Mohty M. Relapsed refractory multiple myeloma: A comprehensive overview. Leukemia. 2019;33:2343–2357. doi: 10.1038/s41375-019-0561-2.
    1. Tai Y.-T., Anderson K.C. B cell maturation antigen (BCMA)-based immunotherapy for multiple myeloma. Expert Opin. Biol. Ther. 2019;19:1143–1156. doi: 10.1080/14712598.2019.1641196.
    1. Burwick N., Sharma S. Glucocorticoids in multiple myeloma: Past, present, and future. Ann. Hematol. 2019;98:19–28. doi: 10.1007/s00277-018-3465-8.
    1. Swan D., Gurney M., Krawczyk J., Ryan A.E., O’Dwyer M. Beyond DNA Damage: Exploring the Immunomodulatory Effects of Cyclophosphamide in Multiple Myeloma. Hemasphere. 2020;4:e350.
    1. Gabizon A.A., Patil Y., La-Beck N.M. New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy. Drug Resist. Updat. 2016;29:90–106. doi: 10.1016/j.drup.2016.10.003.
    1. Kuczma M., Ding Z.-C., Zhou G. Immunostimulatory Effects of Melphalan and Usefulness in Adoptive Cell Therapy with Antitumor CD4+ T Cells. Crit. Rev. Immunol. 2016;36:179–191. doi: 10.1615/CritRevImmunol.2016017507.
    1. Esma F., Salvini M., Troia R., Boccadoro M., LaRocca A., Pautasso C. Melphalan hydrochloride for the treatment of multiple myeloma. Expert Opin. Pharmacother. 2017;18:1127–1136. doi: 10.1080/14656566.2017.1349102.
    1. Palumbo A., Offidani M., Patriarca F., Petrucci M.T., Cavo M. Bendamustine for the treatment of multiple myeloma in first-line and relapsed–refractory settings: A review of clinical trial data. Leuk. Lymphoma. 2014;56:559–567. doi: 10.3109/10428194.2014.915545.
    1. Offidani M., Corvatta L., Maracci L., Liberati A.M., Ballanti S., Attolico I., Caraffa P., Alesiani F., Di Toritto T.C., Gentili S., et al. Efficacy and tolerability of bendamustine, bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: A phase II study. Blood Cancer J. 2013;3:e162. doi: 10.1038/bcj.2013.58.
    1. Latif T., Chauhan N., Khan R., Morán A., Usmani S.Z. Thalidomide and its analogues in the treatment of Multiple Myeloma. Exp. Hematol. Oncol. 2012;1:27. doi: 10.1186/2162-3619-1-27.
    1. San-Miguel J., Weisel K., Moreau P., Lacy M., Song K., Delforge M., Karlin L., Goldschmidt H., Banos A., Oriol A., et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): A randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–1066. doi: 10.1016/S1470-2045(13)70380-2.
    1. Moreau P., Weisel K.C., Song K.W., Gibson C.J., Saunders O., Sternas L.A., Hong K., Zaki M.H., Dimopoulos M.A. Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS) Leuk. Lymphoma. 2016;57:2839–2847. doi: 10.1080/10428194.2016.1180685.
    1. Ito T., Handa H. Cereblon as a primary target of IMiDs. Jpn. J. Clin. Hematol. 2019;60:1013–1019. doi: 10.11406/rinketsu.60.1013.
    1. Accardi F., Toscani D., Bolzoni M., Palma B.D., Aversa F., Giuliani N. Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling. BioMed Res. Int. 2015;2015:1–13. doi: 10.1155/2015/172458.
    1. Groen K., Van De Donk N.W.C.J., Stege C., Zweegman S., Nijhof I. Carfilzomib for relapsed and refractory multiple myeloma. Cancer Manag. Res. 2019;11:2663–2675. doi: 10.2147/CMAR.S150653.
    1. Raedler L.A. Ninlaro (Ixazomib): First Oral Proteasome Inhibitor Approved for the Treatment of Patients with Re-lapsed or Refractory Multiple Myeloma. Am. Health Drug Benefits. 2016;9:102–105.
    1. Narayanan S., Cai C.-Y., Assaraf Y.G., Guo H.-Q., Cui Q., Wei L., Huang J.-J., Ashby C.R., Chen Z.-S. Targeting the ubiquitin-proteasome pathway to overcome anti-cancer drug resistance. Drug Resist. Updat. 2020;48:100663. doi: 10.1016/j.drup.2019.100663.
    1. Eleutherakis-Papaiakovou E., Kanellias N., Kastritis E., Gavriatopoulou M., Terpos E., Dimopoulos M.A. Efficacy of Panobinostat for the Treatment of Multiple Myeloma. J. Oncol. 2020;2020:1–11. doi: 10.1155/2020/7131802.
    1. Bringhen S., De Wit E., Dimopoulos M.-A. New Agents in Multiple Myeloma: An Examination of Safety Profiles. Clin. Lymphoma Myeloma Leuk. 2017;17:391–407.e5. doi: 10.1016/j.clml.2017.05.003.
    1. Yee A.J., Bensinger W.I., Supko J.G., Voorhees P.M., Berdeja J.G., Richardson P.G., Libby E.N., Wallace E.E., Birrer N.E., Burke J.N., et al. Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A multicentre phase 1b trial. Lancet Oncol. 2016;17:1569–1578. doi: 10.1016/S1470-2045(16)30375-8.
    1. Vogl D.T., Raje N., Jagannath S., Richardson P., Hari P., Orlowski R., Supko J.G., Tamang D., Yang M., Jones S.S., et al. Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma. Clin. Cancer Res. 2017;23:3307–3315. doi: 10.1158/1078-0432.CCR-16-2526.
    1. Pulya S., Amin S.A., Adhikari N., Biswas S., Jha T., Ghosh B. HDAC6 as privileged target in drug discovery: A perspective. Pharmacol. Res. 2020;163:105274. doi: 10.1016/j.phrs.2020.105274.
    1. Nooka A.K., Kaufman J.L., Hofmeister C.C., Joseph N.S., Heffner T.L., Gupta V.A., Sullivan H.C., Neish A.S., Dhodapkar M.V., Lonial S. Daratumumab in multiple myeloma. Cancer. 2019;125:2364–2382. doi: 10.1002/cncr.32065.
    1. Lonial S., Vij R., Harousseau J.-L., Facon T., Moreau P., Mazumder A., Kaufman J.L., Leleu X., Tsao L.C., Westland C., et al. Elotuzumab in Combination With Lenalidomide and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma. J. Clin. Oncol. 2012;30:1953–1959. doi: 10.1200/JCO.2011.37.2649.
    1. Richardson P.G., Jagannath S., Moreau P., Jakubowiak A.J., Raab M.S., Facon T., Vij R., White D., Reece D.E., Benboubker L., et al. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: Final phase 2 results from the randomised, open-label, phase 1b–2 dose-escalation study. Lancet Haematol. 2015;2:e516–e527. doi: 10.1016/S2352-3026(15)00197-0.
    1. Yee A.J., Raje N.S. Denosumab for the treatment of bone disease in solid tumors and multiple myeloma. Future Oncol. 2018;14:195–203. doi: 10.2217/fon-2017-0403.
    1. Varga C., Laubach J.P., Anderson K.C., Richardson P.G. Investigational agents in immunotherapy: A new horizon for the treatment of multiple myeloma. Br. J. Haematol. 2018;181:433–446. doi: 10.1111/bjh.15116.
    1. Moreno L., Perez C., Zabaleta A., Manrique I., Alignani D., Ajona D., Blanco L., Lasa M., Maiso P., Rodriguez I., et al. The Mechanism of Action of the Anti-CD38 Monoclonal Antibody Isatuximab in Multiple Myeloma. Clin. Cancer Res. 2019;25:3176–3187. doi: 10.1158/1078-0432.CCR-18-1597.
    1. Van De Donk N.W., Usmani S.Z. CD38 Antibodies in Multiple Myeloma: Mechanisms of Action and Modes of Resistance. Front. Immunol. 2018;9:2134. doi: 10.3389/fimmu.2018.02134.
    1. Jelinek T., Paiva B., Hajek R. Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma. Front. Immunol. 2018;9:2431. doi: 10.3389/fimmu.2018.02431.
    1. Boussi L., Niesvizky R. Advances in immunotherapy in multiple myeloma. Curr. Opin. Oncol. 2017;29:460–466. doi: 10.1097/CCO.0000000000000407.
    1. Topp M.S., Duell J., Zugmaier G., Attal M., Moreau P., Langer C., Krönke J., Facon T., Salnikov A.V., Lesley R., et al. Anti–B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma. J. Clin. Oncol. 2020;38:775–783. doi: 10.1200/JCO.19.02657.
    1. Cohen A.D., Raje N., Fowler J.A., Mezzi K., Scott E.C., Dhodapkar M.V. How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma. Clin. Cancer Res. 2020;26:1541–1554. doi: 10.1158/1078-0432.CCR-19-2111.
    1. Lin Q., Zhao J., Song Y., Liu D. Recent updates on CAR T clinical trials for multiple myeloma. Mol. Cancer. 2019;18:1–11. doi: 10.1186/s12943-019-1092-1.
    1. Khoury H.J., Garcia-Manero G., Borthakur G., Kadia T., Foudray M.C., Arellano M., Langston A., Bethelmie-Bryan B., Rush S., Litwiler K., et al. A phase 1 dose-escalation study of ARRY-520, a kinesin spindle protein in-hibitor, in patients with advanced myeloid leukemias: ARRY-520 in Advanced Leukemias. Cancer. 2012;118:3556–3564. doi: 10.1002/cncr.26664.
    1. Shah J.J., Kaufman J.L., Zonder J.A., Cohen A.D., Bensinger W.I., Hilder B.W., Rush S.A., Walher D.H., Tunquist B.J., Litwiler K.S., et al. A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexame-thasone in relapsed/refractory multiple myeloma: Filanesib ± Dex in Multiple Myeloma. Cancer. 2017;123:4617–4630. doi: 10.1002/cncr.30892.
    1. Vaxman I., Sidiqi M.H., Gertz M.A. Venetoclax for the treatment of multiple myeloma. Expert Rev. Hematol. 2018;11:915–920. doi: 10.1080/17474086.2018.1548931.
    1. Podar K., Shah J., Chari A., Richardson P.G., Jagannath S. Selinexor for the treatment of multiple myeloma. Expert Opin. Pharmacother. 2020;21:399–408. doi: 10.1080/14656566.2019.1707184.
    1. Lonial S., Lee H.C., Badros A., Trudel S., Nooka A.K., Chari A., Abdallah A.-O., Callander N., Lendvai N., Sborov D., et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): A two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21:207–221. doi: 10.1016/S1470-2045(19)30788-0.
    1. Farooq A.V., Degli Esposti S., Popat R., Thulasi P., Lonial S., Nooka A.K., Jakubowiak A., Sborov D., Zaugg B.E., Badros A.Z., et al. Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody–Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Ophthalmol. Ther. 2020;9:889–911. doi: 10.1007/s40123-020-00280-8.
    1. Ailawadhi S., Kelly K.R., Vescio R.A., Jagannath S., Wolf J., Gharibo M., Sher T., Bojanini L., Kirby M., Chanan-Khan A. A Phase I Study to Assess the Safety and Pharmacokinetics of Single-agent Lorvotuzumab Mertansine (IMGN901) in Patients with Relapsed and/or Refractory CD–56-positive Multiple Myeloma. Clin. Lymphoma Myeloma Leuk. 2019;19:29–34. doi: 10.1016/j.clml.2018.08.018.
    1. Iftikhar A., Hassan H., Iftikhar N., Mushtaq A., Sohail A., Rosko N., Chakraborty R., Razzaq F., Sandeep S., Valent J., et al. Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. Antibodies. 2019;8:34. doi: 10.3390/antib8020034.
    1. Bonello F., Mina R., Boccadoro M., Gay F. Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma. Cancers. 2019;12:15. doi: 10.3390/cancers12010015.
    1. Gavriatopoulou M., Ntanasis-Stathopoulos I., Dimopoulos M.A., Terpos E. Anti-BCMA antibodies in the future management of multiple myeloma. Expert Rev. Anticancer. Ther. 2019;19:319–326. doi: 10.1080/14737140.2019.1586539.
    1. O’Donnell E.K., Raje N.S. New monoclonal antibodies on the horizon in multiple myeloma. Ther. Adv. Hematol. 2016;8:41–53. doi: 10.1177/2040620716682490.
    1. Kinneer K., Flynn M., Thomas S.B., Meekin J., Varkey R., Xiao X., Zhong H., Breen S., Hynes P.G., Fleming R., et al. Preclinical assessment of an antibody–PBD conjugate that targets BCMA on multiple myeloma and myeloma progenitor cells. Leukemia. 2019;33:766–771. doi: 10.1038/s41375-018-0278-7.
    1. Matinkhoo K., Pryyma A., Todorovic M., Patrick B., Perrin D.M. Synthesis of the Death-Cap Mushroom Toxin α-Amanitin. J. Am. Chem. Soc. 2018;140:6513–6517. doi: 10.1021/jacs.7b12698.
    1. Pahl A., Lutz C., Hechler T. Amanitins and their development as a payload for antibody-drug conjugates. Drug Discov. Today Technol. 2018;30:85–89. doi: 10.1016/j.ddtec.2018.08.005.
    1. Zou J., Chen D., Zong Y., Ye S., Tang J., Meng H., An G., Zhang X., Yang L. Immunotherapy based on bispecific T-cell engager with hIgG 1 Fc sequence as a new therapeutic strategy in multiple myeloma. Cancer Sci. 2015;106:512–521. doi: 10.1111/cas.12631.
    1. Chan W.K., Kang S., Youssef Y., Glankler E.N., Barrett E.R., Carter A.M., Ahmed E.H., Prasad A., Chen L., Zhang J., et al. A CS1-NKG2D Bispecific Antibody Collectively Activates Cytolytic Immune Cells against Multiple Myeloma. Cancer Immunol. Res. 2018;6:776–787. doi: 10.1158/2326-6066.CIR-17-0649.
    1. Terpos E., Ntanasis-Stathopoulos I. International Myeloma Society Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2018. Clin. Lymphoma Myeloma Leuk. 2019;19:e324–e336. doi: 10.1016/j.clml.2019.03.008.
    1. Mikhael J.R., Dingli D., Roy V., Reeder C.B., Buadi F.K., Hayman S.R., Dispenzieri A., Fonseca R., Sher T., Kyle R.A., et al. Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013. Mayo Clin. Proc. 2013;88:360–376. doi: 10.1016/j.mayocp.2013.01.019.
    1. Al Hamed R., Bazarbachi A.H., Malard F., Harousseau J.-L., Mohty M. Current status of autologous stem cell transplantation for multiple myeloma. Blood Cancer J. 2019;9:1–10. doi: 10.1038/s41408-019-0205-9.
    1. Durie B.G.M., Hoering A., Abidi M.H., Rajkumar S.V., Epstein J., Kahanic S.P., Thakuri M., Reu F., Reynolds C.M., Sexton R., et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): A randomised, open-label, phase 3 trial. Lancet. 2017;389:519–527. doi: 10.1016/S0140-6736(16)31594-X.
    1. Arora S., Majhail N.S., Liu H. Hematopoietic Progenitor Cell Mobilization for Autologous Stem Cell Transplantation in Multiple Myeloma in Contemporary Era. Clin. Lymphoma Myeloma Leuk. 2019;19:200–205. doi: 10.1016/j.clml.2018.12.010.
    1. BLENREP-Belantamab Injection, Powder, Lyophilized, for Solution: Highlights of Prescribing Information. Updated 8/2020. GlaxoSmithKline LLC. [(accessed on 21 October 2020)]; Available online: .
    1. FDA Approves GSK’s BLENREP (Belantamab Mafodotin-Blmf) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. GSK. Published 6 August 2020. [(accessed on 6 August 2020)]; Available online:
    1. O’Connor B.P., Raman V.S., Erickson L.D., Cook W.J., Weaver L.K., Ahonen C., Lin L.-L., Mantchev G.T., Bram R.J., Noelle R.J. BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells. J. Exp. Med. 2004;199:91–98. doi: 10.1084/jem.20031330.
    1. Anti-BCMA Therapy Endorsed, despite Eye Toxicity. Cancer Discov. 2020;10:OF2. doi: 10.1158/-NB2020-074.
    1. McMillan A., Warcel D., Popat R. Antibody-drug conjugates for multiple myeloma. Expert Opin. Biol. Ther. 2020:1–13. doi: 10.1080/14712598.2020.1802422.
    1. Drugs and Lactation Database (LactMed) [Internet] Bethesda (MD): National Library of Medicine (US). Belantamab Mafodotin. [(accessed on 17 August 2020)];2006 Available online:
    1. Pereira N.A., Chan K.F., Lin P.C., Song Z. The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity. mAbs. 2018;10:693–711. doi: 10.1080/19420862.2018.1466767.
    1. Trudel S., Lendvai N., Popat R., Voorhees P.M., Reeves B., Libby E.N., Richardson P.G., Anderson L.D., Sutherland H.J., Yong K., et al. Targeting B-cell maturation antigen with GSK2857916 antibody–drug conjugate in relapsed or refractory multiple myeloma (BMA117159): A dose escalation and expansion phase 1 trial. Lancet Oncol. 2018;19:1641–1653. doi: 10.1016/S1470-2045(18)30576-X.
    1. Eaton J.S., Miller P.E., Mannis M.J., Murphy C.J. Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials. J. Ocul. Pharmacol. Ther. 2015;31:589–604. doi: 10.1089/jop.2015.0064.
    1. Popat R., Warcel D., O’Nions J., Cowley A., Smith S., Tucker W.R., Yong K., Degli Esposti S. Characterization of response and corneal events with extended follow-up after belantamab mafodotin (GSK2857916) monotherapy for patients with relapsed multiple myeloma: A case series from the first-time-in-human clinical trial. Haematologica. 2020;105:e261–e263. doi: 10.3324/haematol.2019.235937.
    1. Popat R., Suvannasankha A., Kapetanakis V., Prawitz T., Sarri G., Hughes R., Wang F., Hogea C., Ferrante S.A., Willson J. DREAMM-2: Assessing efficacy via indirect comparison of single-agent belantamab mafodotin versus selinexor plus dexamethasone combination in anti-CD38 exposed relapsed/refractory multiple myeloma (RRMM) J. Clin. Oncol. 2020;38:e20527. doi: 10.1200/JCO.2020.38.15_suppl.e20527.
    1. Weisel K., Hopkins T.G., Fecteau D., Bao W., Quigley C., Jewell R.C., Nichols M., Opalinska J. Dreamm-3: A Phase 3, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Monotherapy Compared with Pomalidomide Plus Low-Dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma (RRMM) Blood. 2019;134:1900. doi: 10.1182/blood-2019-129893.
    1. Nooka A.K., Stockerl-Goldstein K., Quach H., Forbes A., Mateos M.-V., Khot A., Tan A., Abonour R., Chopra B., Rogers R., et al. DREAMM-6: Safety and tolerability of belantamab mafodotin in combination with bortezomib/dexamethasone in relapsed/refractory multiple myeloma (RRMM) J. Clin. Oncol. 2020;38:8502. doi: 10.1200/JCO.2020.38.15_suppl.8502.
    1. Longcor J., Oliver K., Friend J., Callandar N. Interim evaluation of a targeted radiotherapeutic, CLR 131, in relapsed/refractory diffuse large B-cell lymphoma patients (R/R DLBCL) Ann. Oncol. 2019;30:v435. doi: 10.1093/annonc/mdz251.
    1. Musto P., La Rocca F. Monoclonal antibodies in relapsed/refractory myeloma: Updated evidence from clinical trials, real-life studies, and meta-analyses. Expert Rev. Hematol. 2020;13:331–349. doi: 10.1080/17474086.2020.1740084.
    1. Richardson P.G., Biswas S., Holkova B., Jackson N., Netherway T., Paul S., Ferron-Brady G., Yeakey A., Shelton C., De Oca R.M., et al. DREAMM-5 platform trial: Belantamab mafodotin in combination with novel agents in patients with relapsed/refractory multiple myeloma (RRMM) J. Clin. Oncol. 2020;38:TPS8552. doi: 10.1200/JCO.2020.38.15_suppl.TPS8552.
    1. Usmani S.Z., Terpos E., Janowski W., Quach H., West S., Williams D., Dettman E.J., Ferron-Brady G., Luptakova K., Gupta I. DREAMM-9: Phase III study of belantamab mafodotin plus VRd versus VRd alone in transplant-ineligible newly diagnosed multiple myeloma (TI NDMM) J. Clin. Oncol. 2020;38:TPS8556. doi: 10.1200/JCO.2020.38.15_suppl.TPS8556.

Source: PubMed

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