First-Line Treatment of Mantle-Cell Lymphoma: Analysis of Effectiveness and Cost-Effectiveness

Aim. To study the correlation between efficacy of mantle-cell lymphoma treatment in clinical practice and failure of first-line therapy and direct expenses depending on the first-line therapy selection. Methods. During the period from 2008 to 2016 a comparative single-center controlled trial was performed to evaluate the effectiveness and toxicity of R-hyper-CVAD-R-HD-AraC (n = 16) regimen. The control group included patients treated with 6–8 cycles of R-CHOP (n = 39). Cytarabine dose was lower than the original regimen and contained not more than 1 g/m2 twice a day for 2 days. R-hyper-CVAD regimen included the standard drug doses. R-HD-AraC treatment started on day 28 from the beginning of the R-hyper-CVAD therapy. The R-hyper-CVAD-R-HD-AraC group consisted of patients with the following characteristics: the median age was 56 years (range 40–66), older than 60 — 6 (38 %), male patients — 12 (75 %), stage IV — 12 (75 %), bulky — 7 (44 %), with bone marrow involved — 11 (69 %), MIPIb high-risk — 8 (50 %), blastoid variant — 7 (44 %). Only 2 patients of the R-hyper-CVAD-R-HD-AraC group received high-dose consolidation treatment with autologous HSC transplantation. HSCT was not performed in the control group. The results of comparative analysis were adjusted to age. In terms of the other significant factors the groups under comparison were similar. Results. All the patients of the study group were treated with 3 R-hyper-CVAD and 3 R-HD-AraC regimens. The rate of complete remission was significantly higher than in the control group —12 (75 %) vs. 14 (36 %). No differences were observed in the 5-year overall survival: 55 % in the R-hyper-CVAD-R-HD-AraC group and 58 % in the R-CHOP group (p = 0.75). Second-line therapy was received by 8 out of 15 (47 %) patients treated with R-hyper-CVAD-R-HD-AraC, and by 18 out of 23 (78 %) patients treated with R-CHOP. Median time before second-line therapy was significantly higher in the R-hyper-CVAD-R-HD-AraC group — 26 vs. 6 months (p = 0.018). The costs of the first and subsequent therapy lines were analysed using a Markov model. Cost analysis of first-line therapy variants to be compared was based on cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER). The analysis proved the cost-effectiveness of R-hyper-CVAD-R-HD-AraC program. Conclusion. R-hyper-CVAD-R-HD-AraC program meets eligibility criteria for effectiveness, toxicity and cost-effectiveness and can, therefore, be recommended as first-line therapy of mantle-cell lymphoma and be used for the further comparative clinical trials