Multiple Myeloma With Amplification of Chr1q: Therapeutic Opportunity and Challenges

Abstract

Multiple myeloma (MM) is an incurable plasma cell malignancy with a heterogeneous genetic background. Each MM subtype may have its own therapeutic vulnerabilities, and tailored therapy could improve outcomes. However, the cumulative frequency of druggable targets across patients is very low, which has precluded the widespread adoption of precision therapy for patients with MM. Amplification of the long arm of chromosome 1 (Amp1q) is one of the most frequent genetic alterations observed in patients with MM, and its presence predicts inferior outcomes in the era of proteasome inhibitors and immunomodulatory agents. Therefore, establishing precision medicine for MM patients with Amp1q stands to benefit a large portion of patients who are otherwise at higher risk of relapse. In this article, we review the prevalence and clinical significance of Amp1q in patients with MM, its pathogenesis and therapeutic vulnerabilities, and discuss the opportunities and challenges for Amp1q-targeted therapy.

Real-world evidence in diagnostics and treatment of patients with multiple myeloma

“…Based on the performed hematological diagnostics, the first relapse of Myeloma multiplex BJ lambda CS IIIA, ISS1, R-ISS1 was confirmed [8,[10][11][12][13][14]. In accordanco with the evolving character of the disease, due to the clonal vulnerability by appearance of amp1q21 in relapse, consequently accompanied with accumulated genetic events, treatment was initiated with bortezomib based triplet VTd in combination with monoclonal antiCD38 antibody, daratumumab (Dara-VTd) from the second cycle of treatment [30,31]. The assessment after two cycles of therapy (I cycle of VTd and I cycle of Dara-VTd) indicated achievement of PR (reduction of 24 h proteinuria 0.1 g/24 and concentration of free lambda light chains 109 mg/l) [21].…”

“…High-risk features of the disease as hypo-secretory immature characteristics with accumulation of genetic abnormalities including amp1q21 and extensive bone disease, indicated the necessity of bortezomib based triplet with immunomodulatory drug in combination with monoclonal antiCD38 antibody, daratumumab [30,34,35]. Previous long-term durable remission may be subject of discussion in terms of MM relapse caused by clonal evolution, or occurrence of new genetic events triggering new MM clone, resulting with the treatment approach as in NDMM patients [30] in Considerine RWE data, treatment decision in RRMM patients should incorporate factors with impact to the patients reported outcomes, such as: patient preferences, physical activity, work productivity, comorbidities, quality of life, disease symptoms/control, treatment-related toxicity, treatment convenience, and so-called "financial toxicity" [36]. Considering treatment choice, RWE data indicates the gap between RCT results and RWE analyses regarding treatment efficacy among triplets of new treatment modalities (bortezomib, carfilzomib, ixazomib, daratumumab) witn a lenalidomide-dexamethasone as backbone [37].…”