Relapsed and refractory multiple myeloma: A systematic review and network meta‐analysis of the efficacy of novel therapies

Abstract

I N TRODUC TIONAdvances in the use of bortezomib as a proteasome inhibitor (PI) and lenalidomide as an immunomodulatory drug (IMID) in early-stage multiple myeloma (MM) therapy have improved both the progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed MM. 1,2 However, all patients eventually relapse and require further treatments. Thus, relapsed/refractory MM (RRMM) is the main challenge of recent clinical research. Specifically, pomalidomide as an IMID, ixazomib or carfilzomib as second-generation PIs, and anti-CD38 (daratumumab and isatuximab) or anti-SLAMF-7 (elotuzumab) monoclonal antibodies are being used in addition to the above drugs, and many combinations of two or three of these agents have been investigated for the treatment of RRMM. Under such circumstances, understanding which regimens are better than others is not easy. The evolving field of treatment options, such as the recently approved agents selinexor (a first-in-class selective inhibitor of nuclear export), melflufen (a peptide-drug conjugate), and venetoclax (a BCL2 inhibitor),

Upregulated Expression of ERBB2/HER2 in Multiple Myeloma as a Predictor of Poor Survival Outcomes

“…We propose a model according to which the observed upregulation of ERB2/HER2 mRNA expression in MM cells is driven transcriptionally by several TFs ( Figure 2 C). The presented data expand our current knowledge regarding the networks of signaling pathways affecting the biology and clinical outcome of MM as well as emerging new molecular targets for chemotherapy-drug-resistant MM [ 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

Clonal Myeloid Dysplasia Following CAR T-Cell Therapy: Chicken or the Egg?

“…Advances in therapy of multiple myeloma (MM) including novel agents such as proteasome inhibitors (PIs) and immunomodulators (IMiDs) as well as anti CD38 antibodies and other advanced therapies greatly improved patient outcomes with profound prolongation of survival [ 1 , 2 ]. This prolonged survival, however, is associated with the risk of developing concurrent or secondary primary malignancies (SPM), the most devastating and treatment-limiting of which are the myeloid malignancies, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).…”

“…Despite major recent advances, the vast majority of MM patients develop resistance to all currently available treatments. In relapsed/refractory (RR) MM [ 2 ], excellent responses have been reported to B-cell maturation antigen (BCMA)-targeting immunotherapy, and specifically to anti-BCMA chimeric antigen receptor T-cell (CART) therapy [ 9 , 12 , 13 , 14 , 15 ]. Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) are the two recently FDA-and EMA-approved anti-BCMA CART-based therapies that induce deep responses (over 85% ORR rates), in heavily pretreated patients [ 16 , 17 ].…”

E-selectin-targeting lipid nanoparticles improve therapeutic efficacy and reduce side effects of bortezomib in multiple myeloma

“…Understanding molecular mechanisms of the cell-signaling pathway in MM cells and the interaction of MM cells with their bone marrow (BM) microenvironment has led to the development of novel therapies [ 2 ]. Despite introducing novel therapies, more than 90% of MM patients relapse due to drug resistance [ 3 ]. The BM microenvironment plays a crucial role in the development of resistance to proteasome inhibitors (PIs) in MM, in which direct and indirect interaction of MM cells with the BM microenvironment induced resistance to PIs in MM [ 4 ].…”