Quality of life in patients with relapsed/refractory multiple myeloma during ixazomib-thalidomide-dexamethasone induction and ixazomib maintenance therapy and comparison to the general population

Abstract This trial evaluated quality of life (QoL) using the EORTC QLQ-C30 and the EORTC QLQ-MY20 instruments in 90 patients with relapsed/refractory multiple myeloma during induction and maintenance therapy with eight cycles of ixazomib-thalidomide-dexamethasone, followed by 12 months of ixazomib maintenance therapy. When patient’s baseline QoL was compared with data of the general population, a significant impairment in health-related QoL, physical, role, and social functioning and several other dimensions, as well as more pain and fatigue, was noted. Induction therapy resulted in significant improvement of pain and worsening of neuropathy, with no significant variation of other parameters. During maintenance treatment, scores for most dimensions including health-related QoL, physical functioning and pain, improved, while for neuropathy no improvement was observed. Time to deterioration (≥10 score points) of health-related QoL, physical functioning, pain, and neuropathy was distinctly shorter than time to progression. Health-related QoL and physical functioning at baseline correlated with overall survival.

[1]  R. Greil,et al.  Ixazomib–Thalidomide–Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma , 2019, British Journal of Cancer.

[2]  M. Dimopoulos,et al.  Health-related quality of life in the ENDEAVOR study: carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed/refractory multiple myeloma , 2019, Blood Cancer Journal.

[3]  A. Gnanasakthy,et al.  A Review of Patient-Reported Outcomes Labeling for Oncology Drugs Approved by the FDA and the EMA (2012-2016). , 2019, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[4]  M. Dimopoulos,et al.  Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial , 2019, The Lancet.

[5]  P. Fayers,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. , 2019, European journal of cancer.

[6]  G. Morgan,et al.  Quality of life during and following sequential treatment of previously untreated patients with multiple myeloma: findings of the Medical Research Council Myeloma IX randomised study , 2018, British Journal of Haematology.

[7]  C. Cleeland,et al.  Patient‐reported health‐related quality of life from the phase III TOURMALINE‐MM1 study of ixazomib‐lenalidomide‐dexamethasone versus placebo‐lenalidomide‐dexamethasone in relapsed/refractory multiple myeloma , 2018, American journal of hematology.

[8]  K. Noonan,et al.  Understanding and treating concerns and symptoms in patients with multiple myeloma , 2017 .

[9]  Paul McCrone,et al.  The eSMART study protocol: a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer , 2017, BMJ Open.

[10]  O. Landgren,et al.  Modern multiple myeloma therapy: deep, sustained treatment response and good clinical outcomes , 2017, Journal of internal medicine.

[11]  M. Dimopoulos,et al.  Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  A. Palumbo,et al.  Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. , 2016, The New England journal of medicine.

[13]  S. Leyvraz,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 , 2015, Haematologica.

[14]  A. Gnanasakthy,et al.  Patient-Reported Outcomes in Cancer Drug Development and US Regulatory Review: Perspectives From Industry, the Food and Drug Administration, and the Patient. , 2015, JAMA oncology.

[15]  Michael L. Wang,et al.  Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. , 2015, The New England journal of medicine.

[16]  T. R. Osborne,et al.  Understanding what matters most to people with multiple myeloma: a qualitative study of views on quality of life , 2014, BMC Cancer.

[17]  P. Sonneveld,et al.  Review of health-related quality of life data in multiple myeloma patients treated with novel agents , 2013, Leukemia.

[18]  D. Esseltine,et al.  Health‐related quality of life in elderly, newly diagnosed multiple myeloma patients treated with VMP vs. MP: results from the VISTA trial , 2012, European journal of haematology.

[19]  P. Fayers,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. , 2012, European journal of cancer.

[20]  R. Fonseca,et al.  Content development for the Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM): use of qualitative and quantitative methods for scale construction. , 2012, Journal of pain and symptom management.

[21]  H. Goldschmidt,et al.  Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myeloma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  K. Strasser-Weippl,et al.  Psychosocial QOL is an independent predictor of overall survival in newly diagnosed patients with multiple myeloma , 2008, European journal of haematology.

[23]  C. Gotay,et al.  The prognostic significance of patient-reported outcomes in cancer clinical trials. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  R. Hájek,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. , 2007, European journal of cancer.

[25]  D. Esseltine,et al.  Patient-reported outcomes helped predict survival in multiple myeloma using partial least squares analysis. , 2007, Journal of clinical epidemiology.

[26]  A. Protopopov,et al.  The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis , 2007, Cancer cell.

[27]  M. Mori,et al.  How accurate is clinician reporting of chemotherapy adverse effects? A comparison with patient-reported symptoms from the Quality-of-Life Questionnaire C30. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  Douglas G Altman,et al.  The logrank test , 2004, BMJ : British Medical Journal.

[29]  D. Machin,et al.  Randomized trials with quality of life endpoints: Are doctors' ratings of patients' physical symptoms interchangeable with patients' self-ratings? , 1997, Quality of Life Research.

[30]  D. Osoba,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. , 1993, Journal of the National Cancer Institute.

[31]  M. Lawton,et al.  Assessment of older people: self-maintaining and instrumental activities of daily living. , 1969, The Gerontologist.

[32]  S. Katz,et al.  STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. , 1963, JAMA.

[33]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[34]  L. Schwartz,et al.  Recommendations for the assessment of progression in randomised cancer treatment trials. , 2009, European journal of cancer.

[35]  D. Osoba,et al.  Analysis and interpretation of health-related quality-of-life data from clinical trials: basic approach of The National Cancer Institute of Canada Clinical Trials Group. , 2005, European journal of cancer.

[36]  P. Viens,et al.  Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy: an issue for quality of care. , 1997, British Journal of Cancer.

[37]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.