**8. Conclusion**

The number of therapeutic options available to treat MM has witnessed a remarkable upsurge since the turn of the current century. The advent of proteasome inhibitors and immunomodulators, in addition to other small molecules working by additional mechanisms, such as histone deacetylase (HDAC) blockade and nuclear export inhibition, has resulted in a major alteration in the clinical approach to the disease. Over the past half-decade, the introduction of mAbs into the fight against this malignancy has further shifted the landscape of how this disease is treated both in newly diagnosed patients and in the relapsed/refractory setting. Chief among these newer entries are daratumumab and elotuzumab, and more recently the anti-CD38 mAb isatuximab and the bispecific antibody belantamab mafodotin. Although employment of mAbs in combination with small molecule agents, such as bortezomib and lenalidomide, has been of immense value in extending patients' ability to achieve deep and durable remissions, relapse and refractoriness to therapy remain as major obstacles to attainment of a cure. Work on checkpoint inhibitors, which have been employed successfully in several tumor types and had shown early promise in MM, continues to move forward in clinical studies of MM, although tempered by recent setbacks stemming from toxicity concerns when used in combination with immunomodulators.

It is evident that future advances in treating MM will be dependent on gaining even deeper insight into the transformative molecular events leading to the disease. As new biomarkers that drive this unrelenting malignancy are identified, design and discovery of innovative target-based therapeutic approaches that will find their way into clinical practice will be established. The attainments already realized by the advent of mAbs, particularly daratumumab, in recent years offers some prospect for even greater success in the application of mAbs in MM over the coming decade.

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**Author details**

Hanley N. Abramson

\*Address all correspondence to: ac2531@wayne.edu

provided the original work is properly cited.

Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Emerging Monoclonal Antibodies for the Treatment of Multiple Myeloma*

*DOI: http://dx.doi.org/10.5772/intechopen.94196*

*Emerging Monoclonal Antibodies for the Treatment of Multiple Myeloma DOI: http://dx.doi.org/10.5772/intechopen.94196*

*Monoclonal Antibodies*

**8. Conclusion**

ICAM-1), and siltuximab (IL-6).

nation with immunomodulators.

coming decade.

Another conjugate linked to a maytansine derivative, the anti-CD56 ADC lorvotuzumab mertansine (IMGN901; BB-10901), had been the focus of a phase I trial in CD56-positive RRMM patients (NCT00346255) but insufficient efficacy and dose-related toxicity reportedly led to discontinuation of further studies of this agent [112, 113]. Other mAbs that have been dropped from further consideration in MM following demonstration of only modest efficacy and/or unacceptable toxicity in trials include the following (target in parentheses): dacetuzumab and lucatumumab (CD40); F50067 (CXCR-4); AVE1642 and figitumumab (IGF-R1); IPH 2101 (KIR); PAT-SM6 (GRP-78); BI 505 (intercellular adhesion molecule-1,

The number of therapeutic options available to treat MM has witnessed a remarkable upsurge since the turn of the current century. The advent of proteasome inhibitors and immunomodulators, in addition to other small molecules working by additional mechanisms, such as histone deacetylase (HDAC) blockade and nuclear export inhibition, has resulted in a major alteration in the clinical approach to the disease. Over the past half-decade, the introduction of mAbs into the fight against this malignancy has further shifted the landscape of how this disease is treated both in newly diagnosed patients and in the relapsed/refractory setting. Chief among these newer entries are daratumumab and elotuzumab, and more recently the anti-CD38 mAb isatuximab and the bispecific antibody belantamab mafodotin. Although employment of mAbs in combination with small molecule agents, such as bortezomib and lenalidomide, has been of immense value in extending patients' ability to achieve deep and durable remissions, relapse and refractoriness to therapy remain as major obstacles to attainment of a cure. Work on checkpoint inhibitors, which have been employed successfully in several tumor types and had shown early promise in MM, continues to move forward in clinical studies of MM, although tempered by recent setbacks stemming from toxicity concerns when used in combi-

It is evident that future advances in treating MM will be dependent on gaining even deeper insight into the transformative molecular events leading to the disease. As new biomarkers that drive this unrelenting malignancy are identified, design and discovery of innovative target-based therapeutic approaches that will find their way into clinical practice will be established. The attainments already realized by the advent of mAbs, particularly daratumumab, in recent years offers some prospect for even greater success in the application of mAbs in MM over the

**148**
