Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group

Gregersen, Henrik; Pečeliūnas, Valdas; Remes, Kari; Schjesvold, Fredrik; Abildgaard, Niels; Nahi, Hareth; Andersen, Niels Frost; Vangsted, Annette Juul; Klausen, Tobias Wirenfeldt; Helleberg, Carsten; Carlson, Kristina; Frølund, Ulf Christian; Axelsson, Per; Stromberg, Olga; Blimark, Cecilie; Crafoord, Jacob; Tsykunova, Galina; Eshøj, Henrik; Waage, Anders; Hansson, Markus; Gulbrandsen, Nina

doi:10.1111/ejh.13709

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…The CARFI trial was a Nordic Myeloma Study Group open-label multi-center, randomized, phase II clinical trial, using a parallel (1:1) group design (clinicaltrials.gov: NCT02572492). Details of the study design, trial treatment and main findings have been published elsewhere [ 30 ]. In brief, patients with MM aged 18 years or more with first relapse after prior ASCT and found eligible for salvage ASCT were included at 25 hospitals within four Nordic countries and Lithuania from January 2015 to April 2018.…”

Section: Methodsmentioning

confidence: 99%

“…To investigate the impact of maintenance therapy after salvage ASCT, the Nordic Myeloma Study Group initiated the CARFI trial in 2015 [ 30 ]. Carfilzomib, a second-generation proteasome inhibitor, was chosen for maintenance therapy in the CARFI trial, administered with dexamethasone every second week.…”

Section: Introductionmentioning

confidence: 99%

“…Carfilzomib, a second-generation proteasome inhibitor, was chosen for maintenance therapy in the CARFI trial, administered with dexamethasone every second week. The primary clinical endpoint of the CARFI study was time to progression; as previously reported, time to progression was significantly prolonged by eight months for the carfilzomib-dexamethasone (Kd) maintenance group (25.1 months) compared to observation (16.7 months) [ 30 ]. HRQL was one of the secondary endpoints of the CARFI trial; results of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire– Core 30 items (QLQ-C30) global health status/quality of life (GHS/QoL) subscale showed no between-group difference during the 2-year follow-up period [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…The primary clinical endpoint of the CARFI study was time to progression; as previously reported, time to progression was significantly prolonged by eight months for the carfilzomib-dexamethasone (Kd) maintenance group (25.1 months) compared to observation (16.7 months) [ 30 ]. HRQL was one of the secondary endpoints of the CARFI trial; results of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire– Core 30 items (QLQ-C30) global health status/quality of life (GHS/QoL) subscale showed no between-group difference during the 2-year follow-up period [ 30 ]. The aim of this paper is to present an in-depth analysis of the CARFI trial PRO endpoints, as per the statistical analysis plan [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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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

Nielsen,

Schjesvold,

Möller

et al. 2024

J Patient Rep Outcomes

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Nielsen,

Schjesvold,

Möller

et al. 2024

J Patient Rep Outcomes

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“…With advances in treatment, it is imperative to continuously assess the role of existing strategies in light of new options. Over the past decade, randomized trials have shown that maintenance treatment after ASCT prolongs PFS, regardless of prior anti‐MM therapy 5–8 . Lenalidomide, a frequently used maintenance drug, has shown beneficial effects on PFS and OS.…”

Section: Introductionmentioning

confidence: 99%

Minimal residual disease status is the prognostic determinant following high‐dose treatment for patients with multiple myeloma

Nahi,

Afram,

Uttervall

et al. 2023

Cancer Medicine

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BackgroundThe presence of minimal residual disease (MRD+) following autologous stem cell transplantation (ASCT) in multiple myeloma represents a poor prognostic factor for progression‐free survival (PFS) and overall survival (OS).MethodsAt our department, we recommend lenalidomide maintenance for patients who are MRD+ after ASCT, while MRD‐negative (MRD−) patients, after information about the national guidelines, were not advised to follow this regimen.ResultsOut of the total 228 patients, 175 received ASCT following first‐line induction (MRD− 92 (53%), MRD+ 83 (47%), at 2 months post‐ASCT), while 53 underwent ASCT after second‐line treatment (MRD− 27 (51%), MRD+ 26 (49%), at the same time point). Comparatively, MRD− patients who did not receive maintenance demonstrated better OS than MRD+ patients who received upfront ASCT and maintenance treatment (96% vs. 86%, p = 0.030, at 3 years). However, nonsignificant difference was found in PFS (76% vs. 62%, at 3 years). Furthermore, second‐line ASCT, MRD− non‐maintained patients exhibited significantly better PFS than MRD+ (71% vs. 27%, p > 0.001, at 3 years). However, OS was better but nonsignificant (96% vs. 76%, at 3 years). Fluorescence in situ hybridization (FISH) analysis was performed on 141 out of the 228 patients. Of these, 85 (60%) patients were deemed standard risk (SR), and 56 (40%) were classified as high risk (HR). In the SR cohort, MRD− patients exhibited better PFS and OS than MRD+ patients (71% vs. 59% and 100% vs. 85%, respectively). In the HR cohort, the MRD− patients showed superior PFS but similar OS compared to MRD+ patients (66% vs. 42% and 81% vs. 80%, respectively).ConclusionsOur results indicate that being MRD− is a more crucial prognostic factor for the 3‐year PFS and OS than the presence of high‐risk cytogenetic markers or undergoing maintenance treatment. The latter appears insufficient, particularly for MRD+ patients following ASCT in the second‐line setting, suggesting that these patients may require a more intensive treatment approach.

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Cellular Immunotherapies for Multiple Myeloma: Current Status, Challenges, and Future Directions

2022

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Multiple myeloma (MM) remains incurable due to relapse, although the use of proteasome inhibitors, immunomodulatory drugs, CD38targeting antibodies, and autologous stem cell transplantation (auto-SCT) significantly improve the clinical outcomes of patients with newly diagnosed MM. In recent years, the introduction of chimeric antigen receptor T-cell (CAR T-cell) therapy has brought hope to patients with refractory and relapsed MM. The graft-versus-myeloma effect of allogeneic SCT provides the possibility for curing a subset of MM patients. In this review, we summarize the recent advances and challenges of cellular immunotherapies for MM, focusing on auto-SCT, allogeneic SCT, and CAR T-cell approaches. We also discuss future directions, and propose a specific algorithm for cellular therapies for MM and probability of minimal residual disease-directed therapy.

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Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group

Cited by 11 publications

References 29 publications

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

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

Minimal residual disease status is the prognostic determinant following high‐dose treatment for patients with multiple myeloma

Cellular Immunotherapies for Multiple Myeloma: Current Status, Challenges, and Future Directions

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