Mutation-dependent treatment approaches for patients with complex multiple myeloma

Abstract

ABSTRACT Introduction: Multiple myeloma is a complex hematologic malignancy that is considered incurable. The increasing comprehension of the genomic complexity has provided new insights into the therapeutic landscape of the disease. Next-generation sequencing studies have identified numerous driver gene mutations and alterations in signaling pathways, implicated in pathobiology and disease progression. Areas covered: Molecular tailored therapies against specific genetic alterations are under development in preclinical studies. These alterations include mutations in BRAF/KRAS/NRAS, FGFR3, overexpression of BCL2, and abberation in pathways such as MYC, JAK/STAT, NFκB, and PI3K/AKT/mTOR. Some of these novel anti-myeloma agents have entered clinical setting, as well. The question of whether these agents should be given as monotherapy or in combination with contemporary regimens is being addressed in ongoing trials. In the current review we present an up-to-date overview of targeted therapies MM. Expert opinion: Although fully personalized MM therapy is nowhere near, new technologies that allow rapid, detailed (and at a feasible cost) evaluation of the genetic content of myeloma on an individual basis may actually allow the development of therapies based on molecular profiling. These regimens may also have the potential to predict prognosis and achieve durable responses when established therapies are unable to overcome drug resistance.