Abstract
Abstract
Background
Decisions regarding maintenance therapy in patients with multiple myeloma should be based on both treatment efficacy and health-related quality of life (HRQL) consequences. In the CARFI trial, patients with first relapse of multiple myeloma underwent salvage autologous stem cell transplantation (salvage ASCT) before randomization to carfilzomib-dexamethasone maintenance therapy (Kd) or observation. The primary clinical endpoint was time to progression, which was extended by 8 months by Kd. The aim of this paper is to present the all HRQL endpoints of the CARFI trial including the HRQL effect of Kd maintenance therapy relative to observation. The primary HRQL endpoint was assessed by EORTC QLQ-C30 Summary score (QLQ-C30-sum) at 8 months follow-up. A key secondary HRQL endpoint was quality-adjusted progression-free-survival (QAPFS).
Methods
HRQL was assessed with EORTC QLQ-C30, EORTC QLQ-MY20 and FACT/GOG-Ntx at randomization and every second month during follow-up. HRQL data were analyzed with linear mixed effect models until 8 months follow-up. QAPFS per individual was calculated by multiplying progression-free survival (PFS) by two quality-adjustment metrics, the QLQ-C30-sum and EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The QAPFS per treatment group was estimated with the Kaplan-Meier method. P < 0.05 was used for statistical significance, and a between-group minimal important difference of 10 points was interpreted as clinically relevant for the QLQ-C30-sum.
Results
168 patients were randomized. HRQL questionnaire compliance was 93%. For the QLQ-C30-sum, the difference of 4.62 points (95% confidence interval (CI) -8.9: -0.4, p = 0.032) was not clinically relevant. PFS was 19.3 months for the Kd maintenance group and 16.8 months for the observation group; difference = 2.5 months (95% CI 0.5; 4.5). QAPFS based on the QLQ-C30-sum for the Kd maintenance group was 18.0 months (95% CI 16.4; 19.6) and for the observation group 15.0 months (95% CI 13.5; 16.5); difference = 3.0 months (95% CI 0.8–5.3). QAPFS based on the QLU-C10D for the Kd maintenance group was 17.5 months (95% CI 15.9; 19.2) and 14.0 months (95% CI 12.4; 15.5) for the observation group; difference = 3.5 months (95% CI 1.1–5.9).
Conclusions
Kd maintenance therapy after salvage ASCT did not adversely affect overall HRQL, but adjustment for HRQL reduced the PFS compared to unadjusted PFS. PFS of maintenance therapy should be quality-adjusted to balance the benefits and HRQL impact.
Funder
University of Southern Denmark
Publisher
Springer Science and Business Media LLC
Subject
Health Information Management,Health Informatics
Reference61 articles.
1. Delgado A, Guddati AK (2021) Clinical endpoints in oncology - a primer. Am J Cancer Res 11(4):1121–1131
2. Bottomley A, Reijneveld JC, Koller M, Flechtner H, Tomaszewski KA, Greimel E (2019) Current state of quality of life and patient-reported outcomes research. Eur J Cancer 121:55–63
3. US Department of Health and Human Services Food and Drug Administration. US Food and Drug Administration. Guidance for industry: patient-reported outcome measures: Use in medical product development to support labeling claims. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM193282.pdf [updated December 2009
4. European Medicine Agency. The use of patientreported outcome (PRO) measures in oncology studies. Appendix 2 to the guideline on the evaluation of anticancer medicinal products in man. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2016/04/WC500205159.pdf2016 [
5. Cella D, Chen CI, Quek RGW, Uribarren A, Reaney M, Mastey V et al (2022) Patient-reported outcomes labeling for oncology drugs: multidisciplinary perspectives on current status and future directions. Front Pharmacol 13:1031992