Background: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies. Methods: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy. Results: Anti-CD38 monoclonal antibodies including daratumumab, isatuximab and MOR202 have shown outstanding results in relapsed and/or refractory multiple myeloma patients. The addition of daratumumab to bortezomib-dexamethasone or lenalidomide-dexamethasone substantially improved patients’ outcome in this patient population. The antiSLAMF7 molecule elotuzumab in combination with lenalidomide-dexamethasone showed to be superior to lenalidomide-dexamethasone alone, without adding meaningful toxicity. Checkpoint blockade therapy in combination with immunomodulatory agents produced objective responses in more than 50% of treated patients. However, this combination was also associated with an increase in toxicity and a thorough safety evaluation is currently ongoing. Conclusion: Monoclonal antibodies are reshaping the standard of care for multiple myeloma and ongoing trials will help physicians to optimize their use in order to further improve patients’ outcome.

Clinical and pharmacologic features of monoclonal antibodies and checkpoint blockade therapy in multiple myeloma

D'Agostino M.
First
;
Gazzera G.;Cetani G.;Bringhen S.;Boccadoro M.;Gay F.
Last
2019

Abstract

Background: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies. Methods: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy. Results: Anti-CD38 monoclonal antibodies including daratumumab, isatuximab and MOR202 have shown outstanding results in relapsed and/or refractory multiple myeloma patients. The addition of daratumumab to bortezomib-dexamethasone or lenalidomide-dexamethasone substantially improved patients’ outcome in this patient population. The antiSLAMF7 molecule elotuzumab in combination with lenalidomide-dexamethasone showed to be superior to lenalidomide-dexamethasone alone, without adding meaningful toxicity. Checkpoint blockade therapy in combination with immunomodulatory agents produced objective responses in more than 50% of treated patients. However, this combination was also associated with an increase in toxicity and a thorough safety evaluation is currently ongoing. Conclusion: Monoclonal antibodies are reshaping the standard of care for multiple myeloma and ongoing trials will help physicians to optimize their use in order to further improve patients’ outcome.
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http://www.eurekaselect.com/162099/article
http://www.eurekaselect.com/article/90374
https://doi.org/10.2174/0929867325666180514114806
CD38; Checkpoint blockade therapy (CBT); Monoclonal antibodies (mAbs); Multiple myeloma (MM); PD-1; PD-L1; SLAMF7; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Humans; Immunologic Factors; Multiple Myeloma
D'Agostino M.; Gazzera G.; Cetani G.; Bringhen S.; Boccadoro M.; Gay F.
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Descrizione: [Restricted access - Published vsn.] D'Agostino M et al. Curr Med Chem . 2019;26(32):5968-5981. doi: 10.2174/0929867325666180514114806. © 2018 Bentham Science Publishers. The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/article/90374 . Available at: http://www.eurekaselect.com/article/90374 | https://doi.org/10.2174/0929867325666180514114806 .
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Descrizione: [Author vsn. - Restricted access] D'Agostino M et al. Curr Med Chem. 2019;26(32):5968-5981. doi: 10.2174/0929867325666180514114806. © 2018 Bentham Science Publishers. The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/article/90374 . The published version is available at: http://www.eurekaselect.com/article/90374 | https://doi.org/10.2174/0929867325666180514114806 .
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Descrizione: [Pre-print vsn.] D'Agostino M et al. Curr Med Chem. 2019;26(32):5968-5981. doi: 10.2174/0929867325666180514114806. © 2018 Bentham Science Publishers. The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/article/90374 . This is not the final published version. The published version is available at: http://www.eurekaselect.com/article/90374 | https://doi.org/10.2174/0929867325666180514114806
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1732895
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