Emerging agents and regimens for multiple myeloma
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REVIEW
Emerging agents and regimens for multiple myeloma Yang Yang1†, Yi Li1†, Huiyao Gu1, Mengmeng Dong1 and Zhen Cai1,2,3*
Abstract The outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal antibodies (MoAb) and stem cell transplantation. However, relapsed and refractory MM (RRMM) remains a major challenge. Novel agents and regimens are under active clinical development. These include new PIs such as ixazomib, marizomib, and oprozomib; new MoAbs such as isatuximab and MOR202; novel epigenetic agent ricolinostat and novel cytokines such as siltuximab. Recently, the first XPO-1 inhibitor, selinexor, was approved for RRMM. BCMA-targeted BiTE, antibody–drug conjugates and CAR-T cells have the potential to revolutionize the therapy for RRMM. In this review, we summarized the latest clinical development of these novel agents and regimens. Keywords: Multiple myeloma, Monoclonal antibody, Immunotherapy, Checkpoint inhibitor, BiTE, CAR-T Background Novel agents and regimens as well as new technologies for tracing minimal residual diseases (MRD) have substantially improved the prognosis of patients with multiple myeloma (MM), with an increase in median survival from 3–5 years to 8–10 years in the past decade [1, 2]. The goal of treatment for newly diagnosed, transplanteligible patients is to achieve the best depth of remission and improve the progression-free survival (PFS) and overall survival (OS). The consensus is that induction therapy followed by autologous stem cell transplantation (ASCT) and maintenance therapy should be the overall management of myeloma, while the quality of life, tolerability, duration of treatment, convenience, and patients’ preference are taken into account [3]. For patients eligible for ASCT, three to four cycles of induction therapy are generally *Correspondence: [email protected] † Yang Yang and Yi Li have contributed equally to this work 1 Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China Full list of author information is available at the end of the article
needed before the mobilization of hematopoietic stem cells. Proteasome inhibitors (PIs) and immunomodulator drugs (IMiDs)-based triplet regimens are preferentially considered, such as bortezomib (BTZ) and lenalidomide (Len) plus dexamethasone (DEX) (VRD), BTZ and thalidomide plus DEX (VTD), or cyclophosphamide and BTZ plus DEX (CyBorD). With better depth of remission and survival [4–6], VRD is currently a standard regimen. The quadruplet regimen of BTZ, Len, cyclophosphamide, and DEX has been found to have increased hematological toxicity but similar efficacy compared to the triplet regimens [7]. Furthermore, with the wide application of cytogenetics-based stratification standards, clinical trials are generally recommended to high-risk patients with the presence of del(17p), translocation t(4;14), t(14;16
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