The current drugs and treatment methods for MM

YearsMain drugs/treatment methodComposition or functionApplication effect
1960Melphalan Cyclophosphamide corticosteroidsAlkylating agent
1990HSCTAutologous hematopoietic stem-cell transplantation.
1990ThalidomideImmunomodulatory; the first drug to show activity in RRMM; the main function is to suppress angiogenesis.Toxic and side effects of the dose on peripheral nerves.
2003BortezomibThe proteasome inhibitor, which inhibits the NF-κB pathway, is often involved in the combined treatment of NDMM and RRMM and triggers “immunogenic” cell death, which can trigger effective anti-MM immune responses and disease control.
2005LenalidomideImmunomodulator that inhibits NF-κB pathway, activates caspase and promotes apoptosis [5]. It is the first-line drug for newly discovered MM. It is mainly involved in immune regulation, suppressing angiogenesis and proliferation.Combined with bortezomib and dexamethasone (VRD), the 4-year overall survival rate was 81%. More than 2% of the patients had grade 3/4 adverse reactions: 63.7% of the patients had blood and lymphatic system diseases, and 13.7% had nervous system diseases [2].
2013PomalidomideImmunomodulator inhibits NF-κB pathway, activates caspase, and promotes apoptosis [5].Currently, it is approved to be combined with dexamethasone, elozumab, and dalatuzumab [3]. The median of PVD and VD was 11.2 and 7.1 (HR = 0.61, 95% CI: 0.49–0.77; P < 0.0001). Hematologic toxicity, gastrointestinal side effects, and rash are common.
2015Daratumumab ElotuzumabMonoclonal antibodies targeting CD38 and slamf7. Treatment of newly discovered and refractory MM.D-RVd improved the complete remission rate and the minimal residual disease (MRD) negative rate, and the single drug remission rate was 29.2% [6]. Grade 3/4 neutropenia: d-RVd/RVD 41.4%, 21.6%; lymphopenia: 23.2%, 21.6%; thrombocytopenia: 16.2%, 8.8% [13].
2015PanobinostatPan-HDAC inhibitor. For RRMM.In combination with bortezomib and dexamethasone, the PFS was significantly improved, but the side effects were significant [11]. The overall response rate was 34.5%, the median time to response was 1.4 months [9]. Thrombocytopenia 63.6%, fatigue, and diarrhea 20.0%. The incidence of serious adverse reactions was 67.3% [9].
2019SelinexorExportin-1 inhibitor specifically blocks xpo1 protein. For the treatment of RRMM, especially grade 3 refractory myelomas.It is often combined with dexamethasone. The median duration of PFS was 13.93 months in the SVD group and 9.46 months in the VD group. This means that the median PFS increased by 4.47 months. Nausea, vomiting, loss of appetite. 73% of patients had thrombocytopenia [10].
2020Isatuximab-irfcThe monoclonal antibody, targeting CD38, is used for RRMM. The immune effect function of MM was restored by blocking immunosuppressive T cells [4].It was combined with pomalidomide/dexamethasone (PD). The median PFS of ISA-PD was 11.5 months, the median PFS of PD was 6.5 months, the HR was 0.60, the ORR of ISA-PD was 60.4%, and the ORR of PD was 35.3% [8]. In monotherapy, infusion response was 51%, fatigue 37%, nausea 32%, upper respiratory tract infection 24% and cough 23% [7]. Non-hematological adverse events caused by is a PD: fatigue 64%, ir40%, upper respiratory tract infection, and cough 40% [12].

HSCT: hematopoietic stem cell transplantation; PFS: progression-free survival; ORR: objective response rate; HR: hazard ratio; NDMM: newly diagnosed MM; PVD: pomalidomide + bortezomib (Velcade) + dexamethasone (DEX); VD: bortezomib (Velcade) + dexamethasone (DEX); D-RVd: daratumumab + lenalidomide (Revlimid) + bortezomib (Velcade) + dexamethasone (DEX); SVD: Selinexor + bortezomib (Velcade) + dexamethasone (DEX); ISA-PD: isatuximab with pomalidomide/dexamethasone; xpo1: exportin 1