COST-EFFECTIVENESS OF POST-AUTOTRANSPLANT LENALIDOMIDE IN PERSONS WITH MULTIPLE MYELOMA.

Main Article Content

Monia Marchetti
Robert Peter Gale
Giovanni Barosi

Keywords

plasma cell myeloma, lenalidomide, autotransplant, cost-effectiveness, decision models

Abstract

Considerable data indicate posttransplant lenalidomide prolongs progression-free survival and probably survival after an autotransplant for plasma cell myeloma (PCM).  However, optimal therapy duration is unknown, controversial and differs in the EU and US.  We compared outcomes and cost-effectiveness of 3 posttransplant lenalidomide strategies in EU and US settings: (1) none; (2) until failure; and (3) 2-year fixed duration.  We used a Markov decision model which included 6 health states and informed by published data.  The model estimated the strategy of lenalidomide given to failure achieved 1.06 quality-adjusted life years (QALYs) at costs per QALY gained of €29,232 in the EU   and $133,401 in the US settings.  Two-year fixed-duration lenalidomide averted €7,286 per QALY gained in the EU setting and saved 0.84 QALYs at $60,835 per QALY gained in the US setting.  These extremely divergent costs per QALY in the EU and US settings resulted from large differences in costs of posttransplant lenalidomide and of 2nd-line therapies driven by whether posttransplant failure was on- or off-lenalidomide.  In Monte Carlo simulation analyses which allowed us to account for variability of inputs, 2-year fixed-duration lenalidomide remained the preferred strategy for improving health-care sustainability in the EU and US settings.

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References

1. Mikhael J, Ismaila N, Cheung N, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol. 2019;37:1228-1263. doi: 10.1200/JCO.18.02096
2. Jain T, Sonbol MB, Firwana B, et al. High-dose chemotherapy with early autologous stem cell transplantation compared to standard dose chemotherapy or delayed transplantation in patient with newly diagnosed multiple myeloma: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2019;25(2):239-247. doi: 10.1016/j.bbmt.2018.09.021
3. Su B, Zhu X, Jiang Y, et al. A meta-analysis of autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent. Leuk Lymphoma. 2019;60(6):1381-1388. doi: 10.1080/10428194.2018.1543874.
4. Dhakal B, Szabo A, Chhabra , et al. Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction: a systematic review and meta-analysis. JAMA Oncology. 2018;4(3):343-350. doi: 10.1001/jamaoncol.2017.4600.
5. Barosi G, Gale RP. Is lenalidomide the standard-of-care after an autotransplant for plasma cell myeloma? Leukemia. 2019;33(3):588-596. doi: 10.1038/s41375-019-0383-2.
6. McCarthy PL, Holtein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017:35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679
7. Holstein SA, Jung SH, Richardson PG, et al. Updated analysis of CALBG (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomized, double-blind, phase 3 trial. Lancet Haematol. 2017;4(9):e431-e442. doi: 10.1016/S2352-3026(17)30140-0.
8. Diamond B, Mclachlan K, Chung DJ, et al. Maintenance therapy and need for cessation studies in multiple myeloma: focus on the future. Best Pract Res Clin Hematol. 2002:33(1):101140. doi: 10.1016/j.beha.2020.101140.
9. Mian I, Milton DR, Shah N, et al. Prolonged survival with a longer duration of maintenance lenalidomide after autologous hematopoietic stem cell transplantation for multiple myeloma. Cancer. 2016;122(24):3831-3837. doi: 10.1002/cncr.30366
10. Jagannath S, Abonous R, Durie BGM, et al. Impact of post-ASCT maintenance therapy on outcomes of patients with newly diagnosed multiple myeloma in Connect MM. Blood Adv. 2018;2(13):1608-1615. doi: 10.1182/bloodadvances.2018017186
11. Fonseca R, Parikh K, Ung B, Ni Q, Argawal A. Maintenance after lenalidomide, bortezomib, and dexamethasone induction with newly diagnosed multiple myeloma and high-risk cytogenetics: an enhanced medical record analysis. HemaSphere. 2018;2:230-231.
12. Cherniawsky H, Sandhu I, Chu M, et al. Lenalidomide maintenance chemotherapy: an analysi of real world data in multiple myeloma patient treated with autologous stem cell transplant and bortezomib-based induction. HemaSphere 2018;2(supplement 2): 968
13. Tay J, Vij R, Norkin M. Impact of active maintenance treatment (MT) compared with no MT on the quality of life (QOL) of patients with multiple myeloma (MM) following first autologous stem cell transplant (ASCT). Blood. 2017; 130 (Supplement 1).
14. Kumar SK, Dispenzeri A, Fraser R, et al. Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time. Leukemia. 2018;32(4):986-995. doi: 10.1038/leu.2017.331
15. Attema AE, Brouwer WBF, Claxton K. Discounting in economic evaluations. Pharmacoeconomics. 2018;36(7):745-758. doi: 10.1007/s40273-018-0672-z
16. Amsler IG, Jeker B, Taleghani BM, et al. Prolonged survival with increasing duration of lenalidomide maintenance after autologous transplant for multiple myeloma. Leukemia Lymphoma. 2019;60(2):511-514. doi: 10.1080/10428194.2018.1473577
17. Offidani M, Morè S, Corvatta L, et al. Factors associated with the probability to skip subsequent lines of therapy: analysis of 321 multiple myeloma (MM) patients in a single tertiary centre. Clin Lymphoma Myeloma Leuk. 2019;19 (supplement 10): e275
18. Dimopoulos MA, San-Miguel J, Belch A, et al. Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Haematologica. 2018;103(12):2088-96. doi: 10.3324/haematol.2018.194282
19. Spencer A, Lentzsch S, Weisel K, et al. Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Haematologica. 2018;103(12): 2079-2087. doi: 10.3324/haematol.2018.194118
20. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carlfizomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015;372(2):142-152. doi: 10.1056/NEJMoa1411321
21. Dimopoulos MA, Moreau P, Palumbo A, et al. Carlfizomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOUR): a randomized, phase 3, open-label, multicenter study. Lancet Oncol. 2016;17(1):27-38. doi: 10.1016/S1470-2045(15)00464-7
22. Richardson PG, Oriol A, Beksac M, et al. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomized, open-label, phase 3 trial. Lancet Oncol. 2019;20(6):781-94. doi: 10.1016/S1470-2045(19)30152-4
23. Moreau P, Joshua D, Chng W-J, et al. Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 2 ENDEAVOR study. Leukemia. 2017;31(1):115-122. doi: 0.1038/leu.2016.186
24. Felix J, Aragao F, Almeida JM, et al. Time-dependent endpoints as predictors of overall survival in multiple myeloma. BMC Cancer. 2013;13:122. 10.1186/1471-2407-13-122.
25. Proskorovsky I, Lewis P, Williams CD, et al. Mapping EORTC QLQ-C30 and QLQ-MY20 to EQ-5D in patients with multiple myeloma. Health Qual Life Outcomes. 2014;12:1–9. doi: 10.1186/1477-7525-12-35.
26. Acaster S, Gaugris S, Velikova G, Yong K, Lloyd A. Impact of the treatment-free interval on health-related quality of life in patients with multiple myeloma: a UK cross-sectional survey. Supportive Care Cancer. 2013;21(2):599-607. doi: 10.1007/s00520-012-1548-y
27. Carlson JJ, Guzauskas GF, Chapman RH, et al. Cost-effectiveness of drugs to treat relapsed/refractory multiple myeloma in the United States. J Manag Care Spec Pharm. 2018;24(1):29-38. doi: 10.18553/jmcp.2018.24.1.29.
28. Hollmann S, Moldaver D, Goyert N, Grima D, Maiese EM. A US cost analysis of triplet regimens for patients with previously treated multiple myeloma. J Manag Care Spec Pharm. 2019;25(4):449-59. doi: 10.18553/jmcp.2019.25.4.449.
29. Zhang TT, Wang S, Wan N, et al. Cost-effectiveness of daratumumab-based triplet therapies in patients with relapsed or refractory multiple myeloma. Clin Ther. 2018;40(7):1122-1139. doi: 10.1016/j.clinthera.2018.05.012
30. Jakubowiak AJ, Houisse I, Majer I, et al. Cost-effectiveness of carlfizomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States. Expert Rev Hematol. 2017;10(2):1107-1119. doi: 10.1080/17474086.2017.1391088.
31. Gonzalez-McQuire S, Young K, Leleu H, et al. Healthcare resource utilization among patients with relapsed multiple myeloma in the UK, France, and Italy. J Med Econ. 2018;21(5):450-467. doi: 10.1080/13696998.2017.1421546
32. Ashcroft J, Judge D, Dhanasiri S, Taylor-Stokes G, Middleton C. Chart review across EU5 in MM post-ASCT patients. Int J Hematol Oncol. 2018;7:IJH05
33. Pelligra CG, Parikh K, Abouzaid S, Ailawadi S. Cost-effectiveness of pomalidomide, carlfizomib, and daratumumab for the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma in the United States. Clin Ther. 2017;398(10):1986–2005. Doi: 10.1016/j.clinthera.2017.08.010
34. Goldschmidt H, Mai EK, Durig J, et al. Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial. Leukemia 2020 (in press https://doi.org/10.1038/s41375-020-0724-1)
35. Olry de Labry Lima A, Gimeno-Ballester V, Rios Tamayo R, et al. Cost-effectiveness of lenalidomide maintenance in patients with multiple myeloma who have undergone autologous transplant of hematopoietic progenitor cells. Bone Marrow Transplant. 2019;54(11):1908-1919. doi: 10.1038/s41409-019-0574-5
36. Zhou Z-Y, Parikh K, Chai X, et al. cost-effectiveness analysis of lenalidomide for maintenance therapy after autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) patients: a United States payer perspective. Blood. 2018;132 (suppl 1).
37. Uyl-de Groot CA, Ramsen R, Boersma J, et al. Lenalidomide as maintenance treatment for patients with newly diagnosed multiple myeloma post-autologous stem cell transplantation: a pharmacoeconomic assessment in the Netherlands. Blood. 2018;132 (suppl 1).
38. Lehners N, Becker N, Benner A, Pritsh M, Lopprich M, Mai EK. Analysis of long-term survival in multiple myeloma after first-line autologous stem cell transplantation: impact of clinical risk factors and sustained response. Cancer Med. 2018;7(2): 307-316. doi: 10.1002/cam4.1283.
39. Bonello F, Pulini S, Ballanti S, et al. Lenalidomide maintenance with or without prednisone in newly diagnosed myeloma patients: a pooled analysis. Cancers (Basel). 2019;11(11):E1735. doi: 10.3390/cancers11111735.
40. Usmani SZ, Hoering A, Cavo M, et al. Clinical predictors of long-term survival in newly diagnosed transplant eligible multiple myeloma – an IMWG Research project. Blood Cancer J. 2018;8(12): 123. Doi: 10.1038/s41408-018-0155-7.
41. Boccadoro M, Usmani SZ, Chari A, et al. A global treatment standard in multiple myeloma (MM) remains elusive despite advances in care over 15 years first results from insight mm, the largest global perspective, observational MM study. HemaSphere. 2018;2; supplement 2 (591-)
42. Hewitt C, Foxon G, Craddy P, Chunara F. ICERs are not all the same. How cost-effectiveness estimates differ beween the UK and US. Value in Health. 2018; 21; supplement 1 (S20-)
43. Marchetti M. Value of innovation for haematologic malignancies. J Med Econ. 2016;19(5):487-489. doi: 10.3111/13696998.2015.1133429
44. Jackson G, Galinsky J, Alderson DEC, et al. Productivity losses in patients with newly diagnosed multiple myeloma following stem cell transplantation and the impact of maintenance therapy. Eur J Haematol. 2019;103(4):393-401. doi: 10.1111/ejh.13298