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01-12-2021 | Multiple Myeloma | Research article

Health-related quality of life in patients with newly diagnosed multiple myeloma ineligible for stem cell transplantation: results from the randomized phase III ALCYONE trial

Authors: Stefan Knop, Maria-Victoria Mateos, Meletios A. Dimopoulos, Kenshi Suzuki, Andrzej Jakubowiak, Chantal Doyen, Paulo Lucio, Zsolt Nagy, Ganna Usenko, Ludek Pour, Mark Cook, Sebastian Grosicki, Andre Crepaldi, Anna Marina Liberati, Philip Campbell, Tatiana Shelekhova, Sung-Soo Yoon, Genadi Losava, Tomoaki Fujisaki, Mamta Garg, Jianping Wang, Susan Wroblewski, Anupa Kudva, Katharine S. Gries, John Fastenau, Jesus San-Miguel, Michele Cavo

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

In the phase III ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) significantly improved overall response rate and progression-free status compared with VMP alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Here, we present patient-reported outcomes (PROs) from ALCYONE.

Methods

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaire were administered at baseline, every 3 months (year 1) and every 6 months (until progression). Treatment effects were assessed using a repeated-measures, mixed-effects model.

Results

Compliance with PRO assessments was comparable at baseline (> 90%) and throughout study (> 76%) for both treatment groups. Improvements from baseline were observed in both groups for EORTC QLQ-C30 Global Health Status (GHS), most functional scales, symptom scales and EQ-5D-5L visual analog scale (VAS). Between-group differences were significant for GHS (p = 0.0240) and VAS (p = 0.0160) at month 3. Improvements in pain were clinically meaningful in both groups at all assessment time points. Cognitive function declined in both groups, but the magnitude of the decline was not clinically meaningful.

Conclusions

Patients with transplant-ineligible NDMM demonstrated early and continuous improvements in health-related quality of life, including improvements in functioning and symptoms, following treatment with D-VMP or VMP.

Trial registration

ClinicalTrials.gov identifier NCT02195479, registered September 21, 2014

Available only for authorised users

Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl 4):iv52–61.CrossRefPubMed

Szabo K, Bodoki L, Nagy-Vincze M, Vincze A, Zilahi E, Szodoray P, et al. Effect of genetic and laboratory findings on clinical course of Antisynthetase syndrome in a Hungarian cohort. Biomed Res Int. 2018;2018:6416378.CrossRefPubMedPubMedCentral

Rodriguez-Otero P, Mateos MV, Martinez-Lopez J, Hernandez MT, Ocio EM, Rosinol L, et al. Predicting long-term disease control in transplant-ineligible patients with multiple myeloma: impact of an MGUS-like signature. Blood Cancer J. 2019;9(4):36. https://doi.org/10.1038/s41408-019-0176-x.CrossRefPubMedPubMedCentral

Moreau P, Attal M, Facon T. Frontline therapy of multiple myeloma. Blood. 2015;125(20):3076–84. https://doi.org/10.1182/blood-2014-09-568915.CrossRefPubMed

Gandolfi S, Vekstein C, Laubach JP, O'Brien A, Masone K, Munshi NC, et al. The evolving role of transplantation in multiple myeloma: the need for a heterogeneous approach to a heterogeneous disease. Clin Adv Hematol Oncol. 2018;16(8):564–74.PubMed

Djebbari F, Sharpley FA, McLain-Smith S, Vallance G, Eyre TA, Kothari J, et al. Treatment-free interval as an additional measure of efficacy in a large UK dataset of transplant ineligible myeloma patients. PLoS One. 2020;15(2):e0229469. https://doi.org/10.1371/journal.pone.0229469.CrossRefPubMedPubMedCentral

Ramsenthaler C, Kane P, Gao W, Siegert RJ, Edmonds PM, Schey SA, et al. Prevalence of symptoms in patients with multiple myeloma: a systematic review and meta-analysis. Eur J Haematol. 2016;97(5):416–29. https://doi.org/10.1111/ejh.12790.CrossRefPubMed

Baz R, Lin HM, Hui AM, Harvey RD, Colson K, Gallop K, et al. Development of a conceptual model to illustrate the impact of multiple myeloma and its treatment on health-related quality of life. Support Care Cancer. 2015;23(9):2789–97. https://doi.org/10.1007/s00520-015-2644-6.CrossRefPubMed

Osborne TR, Ramsenthaler C, Siegert RJ, Edmonds PM, Schey SA, Higginson IJ. What issues matter most to people with multiple myeloma and how well are we measuring them? A systematic review of quality of life tools. Eur J Haematol. 2012;89(6):437–57. https://doi.org/10.1111/ejh.12012.CrossRefPubMed

10.

Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518–28. https://doi.org/10.1056/NEJMoa1714678.CrossRefPubMed

11.

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–76. https://doi.org/10.1093/jnci/85.5.365.CrossRefPubMed

12.

Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727–36. https://doi.org/10.1007/s11136-011-9903-x.CrossRefPubMedPubMedCentral

13.

King MT. A point of minimal important difference (MID): a critique of terminology and methods. Expert Rev Pharmacoecon Outcomes Res. 2011;11(2):171–84. https://doi.org/10.1586/erp.11.9.CrossRefPubMed

14.

Kvam AK, Fayers PM, Wisloff F. Responsiveness and minimal important score differences in quality-of-life questionnaires: a comparison of the EORTC QLQ-C30 cancer-specific questionnaire to the generic utility questionnaires EQ-5D and 15D in patients with multiple myeloma. Eur J Haematol. 2011;87(4):330–7. https://doi.org/10.1111/j.1600-0609.2011.01665.x.CrossRefPubMed

15.

Cocks K, King MT, Velikova G, de Castro GJ, Martyn St-James M, Fayers PM, et al. Evidence-based guidelines for interpreting change scores for the European organisation for the research and treatment of Cancer quality of life questionnaire Core 30. Eur J Cancer. 2012;48(11):1713–21. https://doi.org/10.1016/j.ejca.2012.02.059.CrossRefPubMed

16.

Cocks K, King MT, Velikova G, Fayers PM, Brown JM. Quality, interpretation and presentation of European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 data in randomised controlled trials. Eur J Cancer. 2008;44(13):1793–8. https://doi.org/10.1016/j.ejca.2008.05.008.CrossRefPubMed

17.

Cocks K, King MT, Velikova G, Martyn St-James M, Fayers PM, Brown JM. Evidence-based guidelines for determination of sample size and interpretation of the European organisation for the research and treatment of Cancer quality of life questionnaire Core 30. J Clin Oncol. 2011;29(1):89–96. https://doi.org/10.1200/JCO.2010.28.0107.CrossRefPubMed

18.

Wisløff F, Eika S, Hippe E, Hjorth M, Holmberg E, Kaasa S, et al. Measurement of health-related quality of life in multiple myeloma. Nordic myeloma study group. Br J Haematol. 1996;92(3):604–13. https://doi.org/10.1046/j.1365-2141.1996.352889.x.CrossRefPubMed

19.

Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health Qual Life Outcomes. 2007;5(1):70. https://doi.org/10.1186/1477-7525-5-70.CrossRefPubMedPubMedCentral

20.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.CrossRefPubMed

21.

Coleman EA, Goodwin JA, Coon SK, Richards K, Enderlin C, Kennedy R, et al. Fatigue, sleep, pain, mood, and performance status in patients with multiple myeloma. Cancer Nurs. 2011;34(3):219–27. https://doi.org/10.1097/NCC.0b013e3181f9904d.CrossRefPubMedPubMedCentral

22.

Nielsen LK, Jarden M, Andersen CL, Frederiksen H, Abildgaard N. A systematic review of health-related quality of life in longitudinal studies of myeloma patients. Eur J Haematol. 2017;99(1):3–17. https://doi.org/10.1111/ejh.12882.CrossRefPubMed

23.

Myeloma Trialists' Collaborative Group. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol. 2001;113(4):1020–34. https://doi.org/10.1046/j.1365-2141.2001.02857.x.CrossRef

24.

Schwarz R, Hinz A. Reference data for the quality of life questionnaire EORTC QLQ-C30 in the general German population. Eur J Cancer. 2001;37(11):1345–51. https://doi.org/10.1016/S0959-8049(00)00447-0.CrossRefPubMed

25.

Nolte S, Liegl G, Petersen MA, Aaronson NK, Costantini A, Fayers PM, et al. General population normative data for the EORTC QLQ-C30 health-related quality of life questionnaire based on 15,386 persons across 13 European countries, Canada and the unites states. Eur J Cancer. 2019;107:153–63. https://doi.org/10.1016/j.ejca.2018.11.024.CrossRefPubMed

26.

Robinson D Jr, Esseltine DL, Regnault A, Meunier J, Liu K, van de Velde H. The influence of baseline characteristics and disease stage on health-related quality of life in multiple myeloma: findings from six randomized controlled trials. Br J Haematol. 2016, 174;(3):368–81. https://doi.org/10.1111/bjh.14058.

27.

Jordan K, Proskorovsky I, Lewis P, Ishak J, Payne K, Lordan N, et al. Effect of general symptom level, specific adverse events, treatment patterns, and patient characteristics on health-related quality of life in patients with multiple myeloma: results of a European, multicenter cohort study. Support Care Cancer. 2014;22(2):417–26. https://doi.org/10.1007/s00520-013-1991-4.CrossRefPubMed

28.

Delforge M, Minuk L, Eisenmann JC, Arnulf B, Canepa L, Fragasso A, et al. Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide. Haematologica. 2015;100(6):826–33. https://doi.org/10.3324/haematol.2014.120121.CrossRefPubMedPubMedCentral

29.

Delforge M, Dhawan R, Robinson D Jr, Meunier J, Regnault A, Esseltine DL, et al. Health-related quality of life in elderly, newly diagnosed multiple myeloma patients treated with VMP vs. MP: results from the VISTA trial. Eur J Haematol. 2012;89(1):16–27. https://doi.org/10.1111/j.1600-0609.2012.01788.x.CrossRefPubMed

30.

Dimopoulos MA, Palumbo A, Hajek R, Kropff M, Petrucci MT, Lewis P, et al. Factors that influence health-related quality of life in newly diagnosed patients with multiple myeloma aged ≥ 65 years treated with melphalan, prednisone and lenalidomide followed by lenalidomide maintenance: results of a randomized trial. Leuk Lymphoma. 2014;55(7):1489–97. https://doi.org/10.3109/10428194.2013.847933.CrossRefPubMed

31.

Roussel M, Moreau P, Attal M, Eisenmann JC, Laribi K, Jaccard A, et al. PS1377 improvement in health-related quality of life for newly diagnosed multiple myeloma transplant-eligible patients treated with daratumumab, bortezomib, thalidomide, and dexamethasone: CASSIOPEIA study. HemaSphere. 2019;3(suppl 1):630. https://doi.org/10.1097/01.HS9.0000563784.11014.52.CrossRef

32.

Perrot A, Facon T, Plesner T, Usmani SZ, Kumar S, Bahlis NJ, et al. Faster and sustained improvement in health-related quality of life (HRQoL) for newly diagnosed multiple myeloma (NDMM) patients ineligible for transplant treated with daratumumab, lenalidomide, and dexamethasone (D-Rd) versus Rd alone: MAIA. J Clin Oncol. 2019;37(15):8016. https://doi.org/10.1200/JCO.2019.37.15_suppl.8016.CrossRef

33.

Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020;395(10218):132–41. https://doi.org/10.1016/S0140-6736(19)32956-3.CrossRefPubMed

34.

Terpos E, Kleber M, Engelhardt M, Zweegman S, Gay F, Kastritis E, et al. European myeloma network guidelines for the management of multiple myeloma-related complications. Haematologica. 2015;100(10):1254–66. https://doi.org/10.3324/haematol.2014.117176.CrossRefPubMedPubMedCentral

Title: Health-related quality of life in patients with newly diagnosed multiple myeloma ineligible for stem cell transplantation: results from the randomized phase III ALCYONE trial
Authors: Stefan Knop
Maria-Victoria Mateos
Meletios A. Dimopoulos
Kenshi Suzuki
Andrzej Jakubowiak
Chantal Doyen
Paulo Lucio
Zsolt Nagy
Ganna Usenko
Ludek Pour
Mark Cook
Sebastian Grosicki
Andre Crepaldi
Anna Marina Liberati
Philip Campbell
Tatiana Shelekhova
Sung-Soo Yoon
Genadi Losava
Tomoaki Fujisaki
Mamta Garg
Jianping Wang
Susan Wroblewski
Anupa Kudva
Katharine S. Gries
John Fastenau
Jesus San-Miguel
Michele Cavo
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Multiple Myeloma
Daratumumab
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08325-2

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Abstract

Background

Methods

Results

Conclusions

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