Novel Approaches to Treating Relapsed and Refractory Multiple Myeloma with a Focus on Recent Approvals of Belantamab Mafodotin and Selinexor

Abstract

Though survival outcomes in multiple myeloma patients have improved drastically over the past few decades, there still remains an ongoing need for effective and tolerable treatment options in the relapsed and refractory space. Encouragingly, there have been three recent FDA approvals for triple-class refractory multiple myeloma, and there is promising ongoing development of additional agents with varying novel mechanisms of action. Here, we will review the most recent data on both belantamab mafodotin, an antibody drug conjugate (ADC) targeting BCMA, and selinexor, a first-in-class selective inhibitor of XPO1, as well as touch on some of the recently published data for other immunotherapies in development, namely bispecific T cell engagers, ADCs, and CAR-T cell therapies.

Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP)

“…Belantamab mafodotin (BM) is the first-in-class ADC in MM that utilizes a humanized anti-BCMA mAb linked to the microtubule-disrupting agent monomethyl auristatin F (MMAF) [ 12 ]. It has been recently approved by the FDA and EMA as monotherapy for triple-class refractory MM patients that have previously received four or more therapies [ 2 , 4 , 13 ], including at least one PI, one IMiD, and one anti-CD38 mAb.…”

“…Multiple myeloma (MM) is a hematologic malignancy of terminally differentiated plasma cells (PCs) that currently remains incurable for most patients [1][2][3][4]. Multiple novel treatment options have been introduced over the last two decades, such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 (an antigen on the PCs surface) monoclonal antibodies (mAbs) [1,3,5].…”

Cardiovascular Complications of Modern Multiple Myeloma Therapy: A Pharmacovigilance Study

“…While the initial therapy before newer therapeutic advances has classically consisted of VRd (bortezomib + lenalinomide + dexamethasone) and/or stem cell transplant with bortezomib/lenalinomide maintenance 4 , we have had newer approvals for treatment of multiple myeloma which have received at least one previous regimen. Between 2015-2016, the FDA approved 4 new drugs -elotuzumab (activates NK cells) 5 , ixazomib (proteosome inhibitor) 6 , daratumumab (targeting CD38) 7 , panobinostat(histone deacetylase inhibitor) 8 and more recently belantamab and selinexor in 2020 9,10 . Clinical Daratumumab is frequently used in first line regimens along with VRd as D-VRd 4 .…”

Cardiovascular Complications of Modern Multiple Myeloma Therapy: Analysis of FDA Adverse Event Reporting System

“…While the initial therapy before newer therapeutic advances has classically consisted of VRd (bortezomib + lenalinomide + dexamethasone) and/or stem cell transplant with bortezomib/lenalinomide maintenance(Kumar et al, 2017), we have had newer approvals for treatment of multiple myeloma which have received at least one previous regimen. Between 2015-2016, the FDA approved 4 new drugs – elotuzumab (activates NK cells)(Magen & Muchtar, 2016), ixazomib (proteosome inhibitor)(Raedler, 2016), daratumumab (targeting CD38)(Sanchez, Wang, Siegel, & Wang, 2016), panobinostat(histone deacetylase inhibitor)(Laubach, Moreau, San-Miguel, & Richardson, 2015) and more recently belantamab and selinexor in 2020(Joseph, Tai, Anderson, & Lonial, 2021; Offidani, Corvatta, More, & Olivieri, 2021). Clinical Daratumumab is frequently used in first line regimens along with VRd as D-VRd(Kumar et al, 2017).…”