Organizational and economic aspects of triplet therapy of relapsed/refractory multiple myeloma in the Russian healthcare setting

Background. The introduction of innovative drugs has significantly increased the treatment effectiveness in patients with relapsed/refractory multiple myeloma (RRMM), but the question of whether these expensive options can be financially secured remains open.

Objective: to assess the cost of triplets of targeted drugs ixazomib, carfilzomib, elotuzumab and daratumumab with lenalidomide and dexamethasone used in the treatment of RRMM, and to determine possible payment options for this therapy at the level of the Russian Federation subjects.

Material and methods. The cost of an annual course of treatment with the studied regimens with centralized purchases and the cost of targeted drugs per hospitalization case were calculated based on the maximum registered prices, recommended doses and treatment regimens. The normative legal acts regulating the payment of drug therapy for multiple myeloma were analyzed and possible financing channels and their limitations were identified. Using the example of the Volgograd and Saratov Regions, tariffs under the compulsory medical insurance system were calculated and their sufficiency in covering the cost of targeted therapy was estimated.

Results. The cost of an annual course of triplet therapy per patient in the case of centralized procurement of drugs ranged from 5.51 million rubles (regimen with ixazomib) up to 8.03 million rubles (regimen with carfilzomib). The cost per hospitalization, depending on the number of doses, ranged from 80,667–242,000 rubles (ixazomib, 1–3 doses) in the Saratov Region up to 239,618–958,472 rubles (daratumumab, 1–4 doses) in the Volgograd Region. Possible reimbursement channels are High-Cost Nosologies (HCN), Obligatory Medical Insurance (OMI) and Regional Drug Coverage (RDC) programs, nevertheless triplet therapy cannot be purchased via the single channel and the combination of them is required. It has been shown that, in most cases, the costs for a case of targeted drug treatment in studied regions are covered by the average tariff for the corresponding diagnosis-related group (DRG), except for cases with a maximum duration in a day hospital setting. An analysis of the RDC lists and the procurement of drugs in the studied regimens at the expense of regional budgets showed that lenalidomide, ixazomib, carfilzomib, elotuzumab and daratumumab are included in the restrictive list in regions 77, 74, 66, 63 and 47, but they are purchased only in regions 15, 24, 6, 4 and 6, respectively.

Conclusion. The use of a triplet with ixazomib is characterized by the lowest costs, which indicates its greater economic attractiveness relative to carfilzomib, daratumumab and elotuzumab in the treatment of patients with RRMM. The tariffs established in the current DRG model retain the possibility of paying for treatment with the high-cost medicines at the expense of the OMI funds in combination with the HCN or RDC programs. There are reasons to believe that the expansion of the list of 14 HCN program will increase the provision of patients with highly effective therapy and also reduce the financial burden on the regions.

1. Rubricator of clinical recommendations. Clinical recommendations. Multiple myeloma. ID: 144. 2020. Available at: http://cr.rosminzdrav.ru/schema/144_1 (in Russ.) (accessed 07.06.2021).

2. Moreau P., Masszi T., Grzasko N., et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016; 374 (17): 1621–34. https://doi.org/10.1056/NEJMoa1516282.

3. Stewart K., Rajkumar V., Dimopoulos M., et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015; 372 (2): 142–52. 2015. https://doi.org/10.1056/NEJMoa1411321.

4. Lonial S., Dimopoulos M., Palumbo A., et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015; 373 (7): 621–31. https://doi.org/10.1056/NEJMoa1505654.

5. Dimopoulos M.A., Oriol A., Nahi H., et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016; 375 (14): 1319–31. https://doi.org/10.1056/NEJMoa1607751.

6. van Beurden-Tan C.H., Franken M.G., Blommestein H.M., et al. Systematic literature review and network meta-analysis of treatment outcomes in relapsed and/or refractory multiple myeloma. J Clin Oncol. 2017; 35 (12): 1312–9. https://doi.org/10.1200/JCO.2016.71.1663.

7. Dimopoulos M.A., Kaufman J.L., White D., et al. A comparison of the efficacy of immunomodulatory-containing regimens in relapsed/ refractory multiple myeloma: a network meta-analysis. Clin Lymphoma Myeloma Leuk. 2018; 18 (3): 163–73.e6. https://doi.org/10.1016/j.clml.2017.12.011.

8. State register of maximum selling prices. Available at: https://grls.rosminzdrav.ru/pricelims.aspx (in Russ.) (accessed 07.06.2021).

9. Information on the maximum amounts of wholesale surcharges and the maximum amounts of retail surcharges to the prices of vital and essential medicines established in the subjects of the Russian Federation (data as of 01.04.2021). Available at: https://fas.gov.ru/documents/b-n-ca22dc40-f301-4ea8-863c-c18aa27387a7 (in Russ.) (accessed 07.06.2021).

10. Tax Code of the Russian Federation. Article 164. Tax rates. Available at: http://nalogovyykodeks.ru/statya-164.html (in Russ.) (accessed 07.06.2021).

11. Unified information system in the field of procurement. Available at: https://zakupki.gov.ru/epz/main/public/home.html (in Russ.) (accessed 07.06.2021).

12. State Register of Medicines. Available at: https://grls.rosminzdrav.ru/grls.aspx (in Russ.) (accessed 07.06.2021).

13. Resolution of the Government of the Russian Federation of 28.08.2014 No. 871 (ed. of 03.12.2020) “On approval of the rules for the formation of lists of medicines for medical use and the minimum range of medicines required for the provision of medical care”. Available at: https://base.garant.ru/70728348/ (in Russ.) (accessed 07.06.2021).

14. Protocol of the meeting of the Commission of the Ministry of Health of the Russian Federation on the formation of lists of medicines for medical use and the minimum range of medicines required for the provision of medical care dated 22.04.2021 (in Russ.).

15. Letter of the Ministry of Health of the Russian Federation 11-7/I/2-20691, Federal Compulsory Medical Insurance Fund No. 00-10-26-2-04/11-51 dated 30.12.2020 “Methodological recommendations on ways to pay for medical care at the expense of mandatory medical insurance”. Available at: http://www.ffoms.ru/documents/the-ordersoms (in Russ.) (accessed 07.06.2021).

16. Resolution of the Government of the Saratov Region of 30.12.2020 No. 1073-P “About the territorial program of state guarantees of free provision of medical care to citizens in the Saratov Region for 2021 and for the planning period of 2022 and 2023”. Available at: http://www.sartfoms.ru/normativ/terprog/UPOO_TERPRO2021.pdf (in Russ.) (accessed 07.06.2021).

17. The Law of the Volgograd Region of 26.12.2020 N 130-OD (ed. of 30.03.2021) “On the territorial program of state guarantees of free provision of medical care to citizens in the Volgograd region for 2021 and for the planning period of 2022 and 2023”. Available at: https://docs.cntd.ru/document/571063222 (in Russ.) (accessed 07.06.2021).

18. Tariff agreement on compulsory health insurance in the Saratov Region for 2021. Available at: http://www.sartfoms.ru/tarifagreement/tarif.htm (in Russ.) (accessed 07.06.2021).

19. Tariff agreement on compulsory health insurance in the Volgograd Region for 2021. Available at: https://volgatfoms.ru/anorm_gensogl21.html (in Russ.) (accessed 07.06.2021).

20. Federal Fund for Compulsory Health Insurance. The CHI system of the Russian Federation. Territorial funds. Available at: http://www.ffoms.gov.ru/system-oms/territorial-funds/tsentralnyy-federalnyyokrug (in Russ.) (accessed 07.06.2021).

21. ConsultantPlus. Available at: http://www.consultant.ru (in Russ.) (accessed 07.06.2021).

22. Resolution of the Government of the Russian Federation No. 1416 of 26.11.2018 “On the procedure for organizing the provision of medicines to persons with hemophilia, cystic fibrosis, pituitary nanism, Gaucher disease, malignant neoplasms of lymphoid, hematopoietic and related tissues, multiple sclerosis, hemolytic-uremic syndrome, juvenile arthritis with systemic onset, mucopolysaccharidosis of types I, II and VI, persons after organ and/or tissue transplantation, as well as on the recognition of certain acts of the Government as invalid Russian Federation”. Available at: http://www.garant.ru/products/ipo/prime/doc/72013444 (in Russ.) (accessed 07.06.2021).

23. Order of the Government of the Russian Federation of 12.10.2019 N 2406-r (ed. of 23.11.2020) “On the approval of the list of vital and essential medicines, as well as the lists of medicines for medical use and the minimum range of medicines necessary for the provision of medical care”. Available at: http://www.consultant.ru/document/cons_doc_LAW_335635 (in Russ.) (accessed 07.06.2021).

24. Resolution of the Government of the Russian Federation No. 890 of 30.07.1994 “On state support for the development of the medical industry and improving the provision of medicines and medical products to the population and healthcare institutions” Available at: http://base.garant.ru/101268 (in Russ.) (accessed 07.06.2021).