Abstract:
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. © 2016 by American Society of Clinical Oncology.
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Export Date: 18 February 2017References: Gulbrandsen, N., Hjermstad, M.J., 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 (2004) Eur J Haematol, 72, pp. 172-180;Sonneveld, P., Verelst, S.G., Lewis, P., Review of health-related quality of life data in multiple myeloma patients treated with novel agents (2013) Leukemia, 27, pp. 1959-1969;
Stewart, A.K., Rajkumar, S.V., Dimopoulos, M.A., Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma (2015) N Engl J Med, 372, pp. 142-152;
Aaronson, N.K., Ahmedzai, S., Bergman, B., The European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology (1993) J Natl Cancer Inst, 85, pp. 365-376;
Cocks, K., Cohen, D., Wisløff, F., An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQMY20) in assessing the quality of life of patients with multiple myeloma (2007) Eur J Cancer, 43, pp. 1670-1678;
Kvam, A.K., Fayers, P.M., Wisloff, F., Responsiveness andminimal 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 (2011) Eur J Haematol, 87, pp. 330-337;
Stead, M.L., Brown, J.M., Velikova, G., Development of an EORTC questionnairemodule to be used in health-related quality-of-life assessment for patients with multiple myeloma (1999) Br J Haematol, 104, pp. 605-611;
Wisløff, F., Eika, S., Hippe, E., Measurement of health-related quality of life in multiple myeloma (1996) Br J Haematol, 92, pp. 604-613;
Leleu, X., Petrucci, M.T., Welslau, M., Psychometric performance of the EORTC Quality-of-Life Core questionnaire (QLQ-C30) and QLQ-Multiple Myeloma (QLQ-MY20) in relapsed/refractory multiple myeloma (RRMM) (1721) Blood, 122, p. 2013. , abstr;
Gulbrandsen, N., Wisløff, F., Brinch, L., Healthrelated quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support (2001) Med Oncol, 18, pp. 65-77;
Uyl-De Groot, C.A., Buijt, I., Gloudemans, I.J., Health related quality of life in patients with multiple myeloma undergoing a double transplantation (2005) Eur J Haematol, 74, pp. 136-143;
Wisløff, F., Hjorth, M., Nordic Myeloma Study Group: Health-related quality of life assessed before and during chemotherapy predicts for survival in multiple myeloma (1997) Br J Haematol, 97, pp. 29-37;
Fayers, P.M., Aaronson, N.K., Bjordal, K., (2001) The EORTC QLQ-C30 Scoring Manual, , (ed 3). Brussels, Belgium, European Organisation for Research and Treatment of Cancer;
Mallinckrod, C.H., Lane, P.W., Schnell, D., Recommendations for the primary analysis of continuous endpoints in longitudinal clinical trials (2008) Drug Inf J, 42, pp. 303-319;
Dmitrienko, A., Tamhane, A.C., Bretz, F., (2009) Multiple Testing Problems in Pharmaceutical Statistics, , Boca Raton, FL, CRC Press;
Bell, M.L., Fairclough, D.L., Practical and statistical issues in missing data for longitudinal patient-reported outcomes (2014) Stat Methods Med Res, 23, pp. 440-459;
Hedeker, D., Gibbons, R.D., Application of randomeffects pattern-mixture models for missing data in longitudinal studies (1997) Psychol Methods, 2, pp. 64-78;
Fairclough, D.L., (2002) Design and Analysis of Quality of Life Studies in Clinical Trials, , Boca Raton, FL, Chapman & Hall/CRC;
Thijs, H., Molenberghs, G., Michiels, B., Strategies to fit pattern-mixture models (2002) Biostatistics, 3, pp. 245-265;
Jaeschke, R., Singer, J., Guyatt, G.H., Measurement of health status: Ascertaining the minimal clinically important difference (1989) Control Clin Trials, 10, pp. 407-415;
Cocks, K., King, M.T., Velikova, G., Evidencebased 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 (2011) J Clin Oncol, 29, pp. 89-96;
Delforge, M., Dhawan, R., Robinson, D., Jr., Health-related quality of life in elderly, newly diagnosed multiple myeloma patients treated with VMP vs. MP: Results from the VISTA trial (2012) Eur J Haematol, 89, pp. 16-27;
Nunnally, J., Bernstein, I., (1994) Psychometric Theory, , (ed 3). New York, NY,McGraw-Hill;
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 (2015) 22nd Annual Conference for the International Society for Quality of Life Research, , Presented at Vancouver, British Columbia, Canada, October 21-24;
Cocks, K., King, M.T., Velikova, G., Evidence-based guidelines for interpreting change scores for the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (2012) Eur J Cancer, 48, pp. 1713-1721;
Dimopoulos, M.A., Delforge, M., Hájek, R., Lenalidomide melphalan and prednisone followed by lenalidomide maintenance improves healthrelated quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: Results of a randomized phase III trial (2013) Haematologica, 98, pp. 784-788;
Stephens, M., McKenzie, H., Jordens, C.F., The work of living with a rare cancer: Multiple myeloma (2014) J Adv Nurs, 70, pp. 2800-2809;
Potrata, B., Cavet, J., Blair, S., Understanding distress and distressing experiences in patients living with multiple myeloma: An exploratory study (2011) Psychooncology, 20, pp. 127-134;
Molassiotis, A., Wilson, B., Blair, S., Living with multiple myeloma: Experiences of patients and their informal caregivers (2011) Support Care Cancer, 19, pp. 101-111;
Kvam, A.K., Waage, A., Health-related quality of life in patients with multiple myeloma: Does it matter? (2015) Haematologica, 100, pp. 704-705;
Gadó, K., Domján, G., Quality of Life Issues of Patients with Multiple Myeloma., ,
http://www.intechopen.com/books/multiple-myeloma-a-quickreflection-on-th...
Bell, M.L., Kenward, M.G., Fairclough, D.L., Differential dropout and bias in randomised controlled trials: When it matters and when it may not (2013) BMJ, 346, p. e8668
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