OBJECTIVES: Health-related quality of life (HRQoL) is particularly important during maintenance therapy (MT) in newly diagnosed multiple myeloma post-transplant, when disease symptoms are limited. METHODS: We assessed HRQoL in patients randomised to 26 cycles of MT (ixazomib vs placebo) in TOURMALINE-MM3 (NCT02181413). RESULTS: The characteristics at study entry were well-balanced between ixazomib (n = 386) and placebo (n = 251) arms. At study entry, EORTC QLQ-C30 and MY20 scores were high for functional scales and low for symptom scales and were comparable with those of the general population. Changes in subscale scores across intervals, analysed over 30 four-week intervals using a linear mixed-effects model, were generally small and similar between arms for the EORTC QLQ-C30 Global Health Status/QoL, Physical Functioning, and Pain subscales and EORTC QLQ-MY20 Disease Symptoms subscale and Peripheral Neuropathy item. EORTC QLQ-C30 Nausea/Vomiting and Diarrhoea subscales were consistently worse for ixazomib than for placebo, in line with the ixazomib toxicity profile. Even when least-squares mean differences between arms were statistically significant, none reached the established minimal important clinical difference of 10 in multiple myeloma. CONCLUSIONS: In addition to improvement in progression-free survival with ixazomib, HRQoL was maintained in both arms. Active treatment with ixazomib did not have an adverse impact on HRQoL.

Biostatistics RTI Health Solutions Research Triangle Park NC USA

Department of Clinical Therapeutics Hematology and Medical Oncology School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Hematology Charles University Prague Czech Republic

Department of Hematology Odense University Hospital University of Southern Denmark Odense Denmark

Department of Hematology School of Medicine and Public Health University of Newcastle Waratah New South Wales Australia

Department of Internal Medicine 5 University Medical Hospital and National Center of Tumor Diseases University of Heidelberg Heidelberg Germany

Department of Medicine Hematology Charles University Hospital Hradec Králové Czech Republic

Division of Hematology Department of Internal Medicine Mayo Clinic Rochester MN USA

Global Outcomes Research Takeda Pharmaceuticals Cambridge MA USA

KG Jebsen Center for B cell malignancies University of Oslo Oslo Norway

Oncology Clinical Research Takeda Pharmaceuticals Cambridge MA USA

Oslo Myeloma Center Oslo University Hospital Oslo Norway

Patient Centered Outcomes Assessment RTI Health Solutions Research Triangle Park NC USA

Statistical and Quantitative Sciences Takeda Pharmaceuticals Cambridge MA USA

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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;89:437-457.

Anderson KC, Kyle RA, Rajkumar SV, Stewart AK, Weber D, Richardson P. Clinically relevant end points and new drug approvals for myeloma. Leukemia. 2008;22:231-239.

Lipe B, Vukas R, Mikhael J. The role of maintenance therapy in multiple myeloma. Blood Cancer J. 2016;6(10):e485.

Chakraborty R, Muchtar E, Kumar SK, et al. Outcomes of maintenance therapy with lenalidomide or bortezomib in multiple myeloma in the setting of early autologous stem cell transplantation. Leukemia. 2018;32(3):712-718.

Huang J, Phillips S, Byrne M, et al. Lenalidomide vs bortezomib maintenance choice post-autologous hematopoietic cell transplantation for multiple myeloma. Bone Marrow Transplant. 2018;53(6):701-707.

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(1):IJH05.

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.

Jagannath S, Abonour R, Durie BGM, et al. Impact of post-ASCT maintenance therapy on outcomes in patients with newly diagnosed multiple myeloma in Connect MM. Blood Adv. 2018;2(13):1608-1615.

McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35:3279-3289.

Stewart AK, Trudel S, Bahlis NJ, et al. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinical Trials Group Myeloma 10 Trial. Blood. 2013;121(9):1517-1523.

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.

Sengsayadeth S, Malard F, Savani BN, Garderet L, Mohty M. Posttransplant maintenance therapy in multiple myeloma: the changing landscape. Blood Cancer J. 2017;7(3):e545.

Dimopoulos MA, Gay F, Schjesvold F, et al. TOURMALINE-MM3 study group. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019;393(10168):253-264.

Kvam AK, Wisløff F, Fayers PM. Minimal important differences and response shift in health-related quality of life; a longitudinal study in patients with multiple myeloma. Health Qual Life Outcomes. 2010b;8:79.

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):330-337.

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.

Kvam AK, Fayers P, Wisloff F. What changes in health-related quality of life matter to multiple myeloma patients? A prospective study. Eur J Haematol. 2010;84(4):345-353.

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

EORTC. EORTC QLQ-C30 Scoring Manual. 2001. https://www.eortc.be/qol/files/SCManualQLQ-C30.pdf. Accessed December 15, 2018.

EORTC. Scoring of the EORTC QLQ-C30 summary score. 2018. https://qol.eortc.org/app/uploads/sites/2/2018/02/scoring_of_the_qlq-c30_summary_score.pdf. Accessed December 15, 2018.

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(10):1959-1969.

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(11):1670-1678.

Scott NW, Fayers PM, Aaronson NK, et al. EORTC QLQ-C30 reference values. 2008. http://www.eortc.org/app/uploads/sites/2/2018/02/reference_values_manual2008.pdf. Accessed November 1, 2018.

Gridelli C, de Marinis F, Pujol JL, et al. Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexed versus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2012;7(11):1713-1721.

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(5):784-788.

Abonour R, Durie B, Jagannath S, et al. Health related quality of life of patients with newly diagnosed multiple myeloma receiving any or lenalidomide maintenance after autologous stem cell transplant in the Connect® MM Disease Registry. Blood. 2016;128:537.

Dimopoulos MA, Laubach JP, Echeveste Gutierrez MA, et al. Ixazomib maintenance therapy in newly diagnosed multiple myeloma: an integrated analysis of four phase I/II studies. Eur J Haematol. 2019;102(6):494-503.

Gnanasakthy A, DeMuro C, Clark M, Haydysch E, Ma E, Bonthapally V. Patient-reported outcomes labeling for products approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014). J Clin Onco. 2016;34:1928-1934.

Food and Drug Administration. US Department of Health and Human Services. Guidance for industry, patient-reported outcome measures: use in medical product development to support labeling claims. 2009. https://www.fda.gov/downloads/drugs/guidances/ucm193282.pdf. Accessed November 2, 2018.

Juhasz E, Kim JH, Klingelschmitt G, Walzer S. Effects of erlotinib first-line maintenance therapy versus placebo on the health-related quality of life of patients with metastatic non-small-cell lung cancer. Eur J Cancer. 2013;49:1205-1215.

Quidde J, Hegewisch-Becker S, Graeven U, et al. Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial. Ann Oncol. 2016;27:2203-2210.

Rittmeyer A, Gorbunova V, Vikstrom A, et al. Health-related quality of life in patients with advanced nonsquamous non-small-cell lung cancer receiving bevacizumab or bevacizumab-plus-pemetrexed maintenance therapy in AVAPERL (MO22089). J Thorac Oncol. 2013;8:1409-1416.

Osborne TR, Ramsenthaler C, de Wolf-Linder S, et al. Understanding what matters most to people with multiple myeloma: a qualitative study of views on quality of life. BMC Cancer. 2014;14:496.

Al-Hamadami M, Hashmi SK, Go RS. Use of autologous hematopoietic cell transplantation as initial therapy in multiple myeloma and the impact of socio-geo-demographic factors in the era of novel agents. Am J Hematol. 2014;89:825-830.

Abonour R, Wagner L, Durie BGM, et al. Impact of post-transplantation maintenance therapy on health-related quality of life in patients with multiple myeloma: data from the Connect MM Registry. Ann Hematol. 2018;97:2425-2436.

Chari A, Romanus D, Palumbo A, et al. Randomized clinical trial representativeness and outcomes in real-world patients: comparison of 6 hallmark randomized clinical trials of relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2019;20(1):8-17.

Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41.

Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life

Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

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ClinicalTrials.gov
NCT02181413