The cost-effectiveness of treatment of relapsed/refractory chronic lymphocytic leukemia with a combination of venetoclax and rituximab
Authors: Rudakova Alla V , Strugov Vladimir V 
Published: June 2019

Background. Current treatment of relapsed/refractory chronic lymphocytic leukemia implies the use of regimens that include innovative drugs such as ibrutinib and a combination of venetoclax with rituximab. Herewith the combination of venetoclax with rituximab provides a high rate of eradication of minimal residual disease and, in contrast to ibrutinib, in the standard version it is canceled after 2 years from the start of therapy. Aim. Evaluation of the cost-effectiveness of treatment of relapsed/refractory chronic lymphocytic leukemia with a combination of venetoclax + rituximab and ibrutinib. Materials and methods. The evaluation was carried out from a position of the health care system using the Markov model. The study’s time horizon was 4 years. There were no statistically significant differences in overall and progression-free survival according to data of an indirect comparison of the study MURANO for the combination of venetoclax + rituximab and the studies RESONATE and HELIOS for ibrutinib. Venetoclax price (excluding VAT) used for calculation was corresponded to the manufacturer's price list and it was: film coated tablets, 10 mg №14 - 5830.2 rubles; 50 mg №7 - 14 576.86 rubles; 100 mg №7 - 29 152.65 rubles; 100 mg №14 - 58 306.37 rubles; 100 mg №112 - 466 446.67 rubles. Prices for rituximab and ibrutinib were corresponded to a median of the prices quoted. In all cases the analysis considered VAT and weighted average wholesale surcharge given population size in the Russian Federation. In the base case, costs of therapy after a transition to progression were not considered. When carrying out the sensitivity analysis, the option of monotherapy with venetoclax in patients who had progression on ibrutinib and monotherapy with ibrutinib in patients who had progression on venetoclax + rituximab was also evaluated. As part of the sensitivity analysis, a decrease and increase in the price of venetoclax by 15% and a decrease in the price of ibrutinib by 30% were also evaluated. In addition, an increase in a proportion of patients who moved to progression followed venetoclax withdrawal after 2 years of therapy was evaluated, by 15% per year, as well as a change in a frequency of progression by 15% compared with the base case and a decrease in the study’s time horizon to 3 years. The analysis was performed with discounting at 3.5% per year. Results. The analysis showed that the use of a regimen that includes venetoclax reduces the cost volume by on average of 31.3% compared to ibrutinib (the cost volume for 1 patient per 4 years - 13.341 million rubles and 19.413 million rubles, respectively). The sensitivity analysis demonstrated a reliability of the data obtained (with all analyzed modeling options, including options with an increase in venetoclax price by 15%, a decrease in ibrutinib price by 30% and a decrease in the study’s time horizon to 3 years, the combination of venetoclax + rituximab reduces costs by 1.9-41.0%). Conclusions. Treatment of relapsed / refractory chronic lymphocytic leukemia with a combination of venetoclax and rituximab is comparable in clinical efficacy with ibrutinib monotherapy and can reduce the cost and, therefore, increase the availability of innovative therapy for this group of patients. The main contribution to cost reduction is made by the fact that treatment with venetoclax and rituximab in the absence of progression stops 2 years after the start of treatment, and is not performed until the response is lost, as in the case of ibrutinib.