Abstract
Despite the introduction of novel agents such as proteasome inhibitors, immunomodulatory drugs, and autologous stem cell transplant, multiple myeloma (MM) largely remains an incurable disease. In recent years, monoclonal antibody-based treatment strategies have been developed to target specific surface antigens on MM cells. Treatment with bispecific antibodies (bsAbs) is an immunotherapeutic strategy that leads to an enhanced interaction between MM cells and immune effector cells, e.g., T-cells and natural killer cells. With the immune synapse built by bsAbs, the elimination of MM cells can be facilitated. To date, bsAbs have demonstrated encouraging results in preclinical studies, and clinical trials evaluating bsAbs in patients with MM are ongoing. Early clinical data show the promising efficacy of bsAbs in relapsed/refractory MM. Together with chimeric antigen receptor-modified (CAR)-T-cells, bsAbs represent a new dimension of precision medicine. In this review, we provide an overview of rationale, current clinical development, resistance mechanisms, and future directions of bsAbs in MM.
Highlights
Multiple myeloma (MM) is a plasma cell neoplasia, which is often complicated by osteolytic lesions, anemia, renal dysfunction, hypercalcemia, progressive bone marrow dysfunction, infections, and extramedullary manifestations [1,2]
We have recently reported on our experience with the daratumumab containing five-drug combination therapy “Pom-PAD-Dara”
Our results demonstrated an overall response rate (ORR) of 78% in heavily pretreated patients with RRMM with a manageable safety profile, and patients with penta-refractory MM can benefit from this treatment regimen [16]. monoclonal antibodies (mAbs)-based treatment strategies represent a new dimension of precision medicine in the treatment of MM
Summary
Multiple myeloma (MM) is a plasma cell neoplasia, which is often complicated by osteolytic lesions, anemia, renal dysfunction, hypercalcemia, progressive bone marrow dysfunction, infections, and extramedullary manifestations [1,2]. It has been reported that first-line allogeneic SCT could lead to long-term disease control in patients with high-risk MM through the graft-versus-myeloma effect [4,5,6]. With these developments in the treatment of MM, the five-year relative survival ratios of patients increased from 28% for 1973–1982 to 41% during 2003–2013 [7]. As mAbs are increasingly being used, even for frontline/early treatment lines, the problem of resistance to mAbs emerges and motivates the development of novel immunotherapeutic agents to provide daratumumab and elotuzumab refractory patients with alternative treatment options. We provide an overview of the rationale, current clinical development, resistance mechanisms, and future directions of bsAbs in MM that have, together with CAR-T-cell therapies and immunoconjugates, the potential to pave the way towards a novel era of treatment for MM
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