ABSTRACT: Background: Multiple myeloma (MM) is a heterogeneous disease characterized by chromosomal translocation, deletion, and amplification in plasma cells, resulting in a huge heterogeneity in its outcomes. Of all these cytogenetic abnormalities, Amp1q21 is most commonly detected, which is always associated with significantly shorter progression-free survival (PFS) and overall survival (OS) than normal 1q copy number status. In the era of novel agents such as bortezomib, ixazomib, lenalidomide, a head-to-head comparison of all these agents is still absent, especially in the patients with Amp1q21 alone. So, aiming to explore the optimum therapy to the patients with Amp1q21 only, we conduct this study. Patients and Methods: We searched the PubMed, the Cochrane Library, PMC and the Embase databases, and we selected all the randomized controlled trials (RCTs) in English about MM with Amp1q21 up to April, 2019. A total of 72 papers were full screened and finally 2 literatures can be included in our study. Results: Of the two studies, the one is about IRd (ixazomib, lenalidomide, dexamethasone) vs. placebo-Rd (HR, 0.781; 95% CI, 0.492-1.240), another is about VAD (vincristine, adriamycin, dexamethasone) vs. PAD (bortezomib, adriamycin, dexamethasone) (3-year survival rate: 59% vs. 83%, p=0.016). Conclusion: From this review, MM patients with Amp1q21 may somewhat benefit from ixazomib but the evidence is still stuffless. What's more, a head-to-head comparison between ixazomib and other agents among MM patients with Amp1q21 is also absent. So, we sincerely expect this review can attract some attention for the therapy of this special part of patients. This study was registered in https://www.crd.york.ac.uk/prospero/#recordDetails.