Health-related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial.
Adult
Aged
Antibodies, Monoclonal
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Dexamethasone
/ administration & dosage
Female
Humans
Lenalidomide
/ administration & dosage
Male
Middle Aged
Multiple Myeloma
/ drug therapy
Pain Measurement
Patient Reported Outcome Measures
Progression-Free Survival
Quality of Life
Recurrence
Salvage Therapy
/ psychology
Surveys and Questionnaires
Treatment Outcome
POLLUX
daratumumab
health-related quality of life
patient-reported outcomes
relapsed/refractory multiple myeloma
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
02
12
2020
accepted:
04
03
2021
pubmed:
7
4
2021
medline:
17
12
2021
entrez:
6
4
2021
Statut:
ppublish
Résumé
In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient-reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaires. Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (CIs) derived from a mixed-effects model. PRO assessment compliance rates were high and similar in both D-Rd and Rd groups through cycle 40 (week 156). In this on-treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ-C30 global health status, physical functioning, and pain scores in the D-Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D-Rd treatment. These findings complement the sustained and significant improvement in progression-free survival observed with D-Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009.
Substances chimiques
Antibodies, Monoclonal
0
daratumumab
4Z63YK6E0E
Dexamethasone
7S5I7G3JQL
Lenalidomide
F0P408N6V4
Banques de données
ClinicalTrials.gov
['NCT02076009']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
132-139Informations de copyright
© 2021 British Society for Haematology and John Wiley & Sons Ltd.
Références
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;23:2789-97.
LeBlanc MR, Hirschey R, Leak Bryant A, LeBlanc TW, Smith SK. How are patient-reported outcomes and symptoms being measured in adults with relapsed/refractory multiple myeloma? A systematic review. Qual Life Res. 2019;29:1419-31.
Sonneveld P. Management of multiple myeloma in the relapsed/refractory patient. Hematology Am Soc Hematol Educ Program. 2017;2017:508-17.
de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840-8.
Lammerts van Bueren JJ, Jakobs D, Kaldenhoven N, Roza M, Hiddingh S, Meesters J, et al. Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650984 and Ab79. Blood. 2014;124:3474.
Overdijk MB, Jansen JH, Nederend M, Lammerts van Bueren JJ, Groen RW, Parren PW, et al. The therapeutic CD38 monoclonal antibody daratumumab induces programmed cell death via Fcγ receptor-mediated cross-linking. J Immunol. 2016;197:807-13.
Overdijk MB, Verploegen S, Bogels M, van Egmond M, Lammerts van Bueren JJ, Mutis T, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. mAbs. 2015;7:311-21.
Adams HC 3rd, Stevenaert F, Krejcik J, Van der Borght K, Smets T, Bald J, et al. High-parameter mass cytometry evaluation of relapsed/refractory multiple myeloma patients treated with daratumumab demonstrates immune modulation as a novel mechanism of action. Cytometry A. 2019;95:279-89.
Chiu C, Casneuf T, Axel A, Lysaght A, Bald J, Khokhar NZ, et al. Daratumumab in combination with lenalidomide plus dexamethasone induces clonality increase and T-cell expansion: results from a Phase 3 randomized study (POLLUX). Blood. 2016;128:4531.
Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128:384-94.
Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319-31.
Bahlis NJ, Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, et al. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020;34:1875-84.
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;85:365-76.
EuroQol Group. EuroQol - a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208.
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;87:330-7.
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;5:70.
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;89:16-27.
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;55:1489-97.
Seitzler S, Finley-Oliver E, Simonelli C, Baz R. Quality of life in multiple myeloma: considerations and recommendations. Expert Rev Hematol. 2019;12:419-24.
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 United States. Eur J Cancer. 2019;107:153-63.
EORTC QLQ-C30 reference values. Brussels, Belgium: EORTC Quality of Life Group; 2008. Available from: https://www.eortc.org/app/uploads/sites/2/2018/02/reference_values_manual2008.pdf. Accessed 20 March 2020.
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;174:368-81.
Stewart AK, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hajek R, 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. J Clin Oncol. 2016;34:3921-30.
Leleu X, Masszi T, Bahlis NJ, Viterbo L, Baker B, Gimsing P, 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. Am J Hematol. 2018;93:985-93.
Cella D, McKendrick J, Kudlac A, Palumbo A, Oukessou A, Vij R, et al. Impact of elotuzumab treatment on pain and health-related quality of life in patients with relapsed or refractory multiple myeloma: results from the ELOQUENT-2 study. Ann Hematol. 2018;97:2455-63.
Roydhouse JK, Fiero MH, Kluetz PG. Investigating potential bias in patient-reported outcomes in open-label cancer trials. JAMA Oncol. 2019;5:457-8.