Proteasome inhibitors in the treatment of patients with multiple myeloma of high cytogenetic risk

In recent years, there has been a substantial progress in improving progression-free survival (PFS) and quality of life of multiple myeloma (MM) patients. This has become possible through implementation of novel drugs into clinical practice which were developed on the basis of multiomic molecular genetic studies in MM. The results of these studies also enabled to assess genetic heterogeneity of tumor cells in MM. It was shown that MM patients can have quite different spectra of detected genetic defects in the tumor. The high heterogeneity of multiple myeloma is one of the main reasons for the differences in the effectiveness of drugs. The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. The present review comprehensively discusses the value of some chromosomal aberrations in risk stratification of MM patients. The article analyzes the effectiveness of proteasome inhibitors at high risk of multiple myeloma. In particular, the results of multicenter clinical studies of the efficacy of ixazomib in combination with lenalidomide, pomalidomide, dexamethasone are given. Presented data from patients with MM from the TOURMALINE-MM1/-MM2/-MM3/-MM4 studies on the evaluation of the benefits of ixazomib plus lenalidomide-dexamethasone (Rd) against placebo- Rd (TOURMALINE-MM1/-MM2) or ixazomib against placebo (TOURMALINE-MM3/-MM4) at high risk. Ixazomib therapy has drawn attention to a distinct increase in median progression-free survival in patients with high-risk cytogenetic abnormalities and ultrahigh- risk cytogenetic disorders compared to standard risk subgroups.