Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2024-02-01
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| Series: | Journal of Patient-Reported Outcomes |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41687-024-00691-2 |
| _version_ | 1797274444539887616 |
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| author | Lene Kongsgaard Nielsen Fredrik Schjesvold Sören Möller Nina Guldbrandsen Markus Hansson Kari Remes Valdas Peceliunas Niels Abildgaard Henrik Gregersen Madeleine T. King |
| author_facet | Lene Kongsgaard Nielsen Fredrik Schjesvold Sören Möller Nina Guldbrandsen Markus Hansson Kari Remes Valdas Peceliunas Niels Abildgaard Henrik Gregersen Madeleine T. King |
| author_sort | Lene Kongsgaard Nielsen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:58:28Z |
| format | Article |
| id | doaj.art-66aadd268fde4f8ca7e8f753b2c818a7 |
| institution | Directory Open Access Journal |
| issn | 2509-8020 |
| language | English |
| last_indexed | 2024-03-07T14:58:28Z |
| publishDate | 2024-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Journal of Patient-Reported Outcomes |
| spelling | doaj.art-66aadd268fde4f8ca7e8f753b2c818a72024-03-05T19:17:27ZengSpringerOpenJournal of Patient-Reported Outcomes2509-80202024-02-018111810.1186/s41687-024-00691-2Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study GroupLene Kongsgaard Nielsen0Fredrik Schjesvold1Sören Möller2Nina Guldbrandsen3Markus Hansson4Kari Remes5Valdas Peceliunas6Niels Abildgaard7Henrik Gregersen8Madeleine T. King9Quality of life Research Center, Department of Hematology, Odense University HospitalOslo Myeloma Center, Department of Hematology, Oslo University HospitalOpen Patient data Explorative Network, OPEN, Odense University HospitalOslo Myeloma Center, Department of Hematology, Oslo University HospitalDepartment of Hematology, Skåne University HospitalDepartment of Hematology, Turku University HospitalDepartment of Hematology, Vilnius University Hospital Santaros KlinikosQuality of life Research Center, Department of Hematology, Odense University HospitalDepartment of Hematology, Aalborg University HospitalQuality of life Research Center, Department of Hematology, Odense University HospitalAbstract 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.https://doi.org/10.1186/s41687-024-00691-2Randomized clinical trialMultiple myelomaHealth-related quality of lifeCarfilzomib |
| spellingShingle | Lene Kongsgaard Nielsen Fredrik Schjesvold Sören Möller Nina Guldbrandsen Markus Hansson Kari Remes Valdas Peceliunas Niels Abildgaard Henrik Gregersen Madeleine T. King Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group Journal of Patient-Reported Outcomes Randomized clinical trial Multiple myeloma Health-related quality of life Carfilzomib |
| title | Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group |
| title_full | Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group |
| title_fullStr | Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group |
| title_full_unstemmed | Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group |
| title_short | Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group |
| title_sort | health related quality of life and quality adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem cell transplantation in patients with multiple myeloma a randomized phase 2 trial by the nordic myeloma study group |
| topic | Randomized clinical trial Multiple myeloma Health-related quality of life Carfilzomib |
| url | https://doi.org/10.1186/s41687-024-00691-2 |
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