Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.

A Keith Stewart Mayo Clinic Scottsdale AZ; Meletios A Dimopoulos Alexandra Hospital Athens Greece; Tamás Masszi St István and St László Hospital Semmelweis University Budapest Hungary; Ivan Špička General University Hospital Prague Prague; Roman Hájek University Hospital Brno and University of Ostrava Brno Czech Republic; Albert Oriol Institut Català d'Oncologia Institut Josep Carreras Hospital Germans Trias i Pujol; Laura Rosiñol Hospital Clínic de Barcelona Barcelona; Jesus F San Miguel Clinica Universidad de Navarra El Centro de Investigacíon Médica Aplicada Instituto de Investigacíon Sanitaria de Navarra Pamplona Spain; David S Siegel John Theurer Cancer Center at Hackensack University Hackensack NJ; Ruben Niesvizky Weill Cornell Medical College New York NY; Andrzej J Jakubowiak University of Chicago Medicine Chicago IL; Heinz Ludwig Wilhelminen Cancer Research Institute Wilheminenspital Vienna Austria; Jacqui Buchanan Xinqun Yang Biao Xing Naseem Zojwalla and Margaret Tonda Onyx Pharmaceuticals South San Francisco CA; Kim Cocks KCStats Consultancy Leeds United Kingdom; Philippe Moreau University of Nantes Nantes France; and Antonio Palumbo University of Torino Torino Italy

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Gulbrandsen N, Hjermstad MJ, Wisløff F. Interpretation of quality of life scores in multiple myeloma by comparison with a reference population and assessment of the clinical importance of score differences. Eur J Haematol. 2004;72:172–180. PubMed

Sonneveld P, Verelst SG, Lewis P, et al. Review of health-related quality of life data in multiple myeloma patients treated with novel agents. Leukemia. 2013;27:1959–1969. PubMed PMC

Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142–152. PubMed

Aaronson NK, Ahmedzai S, Bergman B, 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;85:365–376. PubMed

Cocks K, Cohen D, Wisløff F, et al. An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQ-MY20) in assessing the quality of life of patients with multiple myeloma. Eur J Cancer. 2007;43:1670–1678. PubMed

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;87:330–337. PubMed

Stead ML, Brown JM, Velikova G, et al. Development of an EORTC questionnaire module to be used in health-related quality-of-life assessment for patients with multiple myeloma. Br J Haematol. 1999;104:605–611. PubMed

Wisløff F, Eika S, Hippe E, et al. Measurement of health-related quality of life in multiple myeloma. Br J Haematol. 1996;92:604–613. PubMed

Leleu X, Petrucci MT, Welslau M, et al: Psychometric performance of the EORTC Quality-of-Life Core questionnaire (QLQ-C30) and QLQ-Multiple Myeloma (QLQ-MY20) in relapsed/refractory multiple myeloma (RRMM). Blood 122, 2013 (abstr 1721)

Gulbrandsen N, Wisløff F, Brinch L, et al. Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support. Med Oncol. 2001;18:65–77. PubMed

Uyl-de Groot CA, Buijt I, Gloudemans IJ, et al. Health related quality of life in patients with multiple myeloma undergoing a double transplantation. Eur J Haematol. 2005;74:136–143. PubMed

Wisløff F, Hjorth M, Nordic Myeloma Study Group Health-related quality of life assessed before and during chemotherapy predicts for survival in multiple myeloma. Br J Haematol. 1997;97:29–37. PubMed

Fayers PM, Aaronson NK, Bjordal K, et al. The EORTC QLQ-C30 Scoring Manual. (ed 3). Brussels, Belgium: European Organisation for Research and Treatment of Cancer; 2001.

Mallinckrod CH, Lane PW, Schnell D, et al. Recommendations for the primary analysis of continuous endpoints in longitudinal clinical trials. Drug Inf J. 2008;42:303–319.

Dmitrienko A, Tamhane AC, Bretz F (eds): Multiple Testing Problems in Pharmaceutical Statistics. Boca Raton, FL, CRC Press, 2009.

Bell ML, Fairclough DL. Practical and statistical issues in missing data for longitudinal patient-reported outcomes. Stat Methods Med Res. 2014;23:440–459. PubMed

Hedeker D, Gibbons RD. Application of random-effects pattern-mixture models for missing data in longitudinal studies. Psychol Methods. 1997;2:64–78.

Fairclough DL. Design and Analysis of Quality of Life Studies in Clinical Trials. Boca Raton, FL: Chapman & Hall/CRC; 2002.

Thijs H, Molenberghs G, Michiels B, et al. Strategies to fit pattern-mixture models. Biostatistics. 2002;3:245–265. PubMed

Jaeschke R, Singer J, Guyatt GH. Measurement of health status: Ascertaining the minimal clinically important difference. Control Clin Trials. 1989;10:407–415. PubMed

Cocks K, King MT, Velikova G, et al. 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;29:89–96. PubMed

Delforge M, Dhawan R, Robinson D, Jr, 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;89:16–27. PubMed

Nunnally J, Bernstein I. Psychometric Theory. (ed 3). New York, NY: McGraw-Hill; 1994.

Cocks K, Buchanan J: Defining responders on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (30-item core module) (QLQ-C30) subscales. Presented at 22nd Annual Conference for the International Society for Quality of Life Research, Vancouver, British Columbia, Canada, October 21-24, 2015.

Cocks K, King MT, Velikova G, 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;48:1713–1721. PubMed

Dimopoulos MA, Delforge M, Hájek R, et al. Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: Results of a randomized phase III trial. Haematologica. 2013;98:784–788. PubMed PMC

Stephens M, McKenzie H, Jordens CF. The work of living with a rare cancer: Multiple myeloma. J Adv Nurs. 2014;70:2800–2809. PubMed

Potrata B, Cavet J, Blair S, et al. Understanding distress and distressing experiences in patients living with multiple myeloma: An exploratory study. Psychooncology. 2011;20:127–134. PubMed

Molassiotis A, Wilson B, Blair S, et al. Living with multiple myeloma: Experiences of patients and their informal caregivers. Support Care Cancer. 2011;19:101–111. PubMed

Kvam AK, Waage A. Health-related quality of life in patients with multiple myeloma: Does it matter? Haematologica. 2015;100:704–705. PubMed PMC

Gadó K, Domján G: Quality of life issues of patients with multiple myeloma. http://www.intechopen.com/books/multiple-myeloma-a-quick-reflection-on-the-fast-progress/quality-of-life-issues-of-patients-with-multiple-myeloma.

Bell ML, Kenward MG, Fairclough DL, et al. Differential dropout and bias in randomised controlled trials: When it matters and when it may not. BMJ. 2013;346:e8668. PubMed PMC

Health-related quality of life in the ENDEAVOR study: carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed/refractory multiple myeloma

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

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