Clinical and Genetic Aspects of the Refractory Forms of Multiple Myeloma

Abstract

Treatment of multiple myeloma has progressed significantly over the past years after the introduction of immunomodulation drugs and proteasome inhibitors, which lead to the overall survival improvement, but still disease has exacerbations (relapses) and remissions. All patients with multiple myeloma have relapses within different interval of time. The duration of achieved remission in patients with a relapse of multiple myeloma becomes shorter with each subsequent case. The choice of regimen for relapse of multiple myeloma is very difficult. It depends on a number of factors, including the previous induction regimen, the number of lines of the previous therapy, and the degree of aggression of relapse. The article is dedicated to the peculiarities of drug resistance development to the first line therapy in patients with multiple myeloma by assessing of genetic markers (deletion variants of GSTT1, GSTM1 genes, GSTP1 (А313G), MDR1 (C3435T)) and clinical-hematological, laboratory characteristics.The objective: to develop the predictive algorithm for the effectiveness of treatment in patients multiple myeloma by assessing of clinical genetic and laboratory parameters.Materials and methods. 68 clinical and laboratory indexes and genetic markers (deletion polymorphism of genes GSTT1, GSTM1, polymorphism А313G, C3435T genes GSTP1, MDR1) was studied in 130 patients with multiple myeloma.Results. It was determined that important predictors of development of refractory forms of multiple myeloma is allelic polymorphism of gene GSTM1, higher level α2-globulin and calcium in blood serum at the disease beginning.Conclusions. Implementation of predicative algorithm based on assessment of GSTM1-polymorphism, level of α2-globulin and calcium in blood serum before the beginning of treatment raises efficacy of evaluation of individual prognosis for response on treatment.