Lenalidomide-dexamethasone (Rd) is standard treatment for elderly patients with multiple myeloma (MM). In this randomized phase 3 study, we investigated efficacy and feasibility of dose/schedule-adjusted Rd followed by maintenance at 10 mg per day without dexamethasone (Rd-R) vs continuous Rd in elderly, intermediate-fit newly diagnosed patients with MM. Primary end point was event-free survival (EFS), defined as progression/death from any cause, lenalidomide discontinuation, or hematologic grade 4 or nonhematologic grade 3 to 4 adverse event (AE). Of 199 evaluable patients, 101 received Rd-R and 98 continuous Rd. Median follow-up was 37 months. EFS was 10.4 vs 6.9 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.95; P = .02); median progression-free survival, 20.2 vs 18.3 months (HR, 0.78; 95% CI, 0.55-1.10; P = .16); and 3-year overall survival, 74% vs 63% (HR, 0.62; 95% CI, 0.37-1.03; P = .06) with Rd-R vs Rd, respectively. Rate of ≥1 nonhematologic grade ≥3 AE was 33% vs 43% (P = .14) in Rd-R vs Rd groups, with neutropenia (21% vs 18%), infections (10% vs 12%), and skin disorders (7% vs 3%) the most frequent; constitutional and central nervous system AEs mainly related to dexamethasone were more frequent with Rd. Lenalidomide was discontinued for AEs in 24% vs 30% and reduced in 45% vs 62% of patients receiving Rd-R vs Rd, respectively. In intermediate-fit patients, switching to reduced-dose lenalidomide maintenance without dexamethasone after 9 Rd cycles was feasible, with similar outcomes to standard continuous Rd. This trial was registered at www.clinicaltrials.gov as #NCT02215980.

Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma

Larocca, Alessandra
First
;
Bonello, Francesca;D'Agostino, Mattia;Capra, Andrea;Boccadoro, Mario;Bringhen, Sara
Last
2021

Abstract

Lenalidomide-dexamethasone (Rd) is standard treatment for elderly patients with multiple myeloma (MM). In this randomized phase 3 study, we investigated efficacy and feasibility of dose/schedule-adjusted Rd followed by maintenance at 10 mg per day without dexamethasone (Rd-R) vs continuous Rd in elderly, intermediate-fit newly diagnosed patients with MM. Primary end point was event-free survival (EFS), defined as progression/death from any cause, lenalidomide discontinuation, or hematologic grade 4 or nonhematologic grade 3 to 4 adverse event (AE). Of 199 evaluable patients, 101 received Rd-R and 98 continuous Rd. Median follow-up was 37 months. EFS was 10.4 vs 6.9 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.95; P = .02); median progression-free survival, 20.2 vs 18.3 months (HR, 0.78; 95% CI, 0.55-1.10; P = .16); and 3-year overall survival, 74% vs 63% (HR, 0.62; 95% CI, 0.37-1.03; P = .06) with Rd-R vs Rd, respectively. Rate of ≥1 nonhematologic grade ≥3 AE was 33% vs 43% (P = .14) in Rd-R vs Rd groups, with neutropenia (21% vs 18%), infections (10% vs 12%), and skin disorders (7% vs 3%) the most frequent; constitutional and central nervous system AEs mainly related to dexamethasone were more frequent with Rd. Lenalidomide was discontinued for AEs in 24% vs 30% and reduced in 45% vs 62% of patients receiving Rd-R vs Rd, respectively. In intermediate-fit patients, switching to reduced-dose lenalidomide maintenance without dexamethasone after 9 Rd cycles was feasible, with similar outcomes to standard continuous Rd. This trial was registered at www.clinicaltrials.gov as #NCT02215980.
137
22
3027
3036
https://ashpublications.org/blood/article/137/22/3027/475576/Dose-schedule-adjusted-Rd-R-vs-continuous-Rd-for
https://doi.org/10.1182/blood.2020009507
https://air.unimi.it/handle/2434/841520
https://air.unimi.it/retrieve/dfa8b9a6-ec6e-748b-e053-3a05fe0a3a96/blood.2020009507.pdf
Larocca, Alessandra; Bonello, Francesca; Gaidano, Gianluca; D'Agostino, Mattia; Offidani, Massimo; Cascavilla, Nicola; Capra, Andrea; Benevolo, Giulia; Tosi, Patrizia; Galli, Monica; Marasca, Roberto; Giuliani, Nicola; Bernardini, Annalisa; Antonioli, Elisabetta; Rota-Scalabrini, Delia; Cellini, Claudia; Pompa, Alessandra; Monaco, Federico; Patriarca, Francesca; Caravita di Toritto, Tommaso; Corradini, Paolo; Tacchetti, Paola; Boccadoro, Mario; Bringhen, Sara
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Descrizione: [Restricted access - PUBLISHED Vsn.] Larocca A et al. Blood. 2021 Jun 3;137(22):3027-3036. doi: 10.1182/blood.2020009507. PMID: 33739404. © 2021 by The American Society of Hematology. Available at: https://ashpublications.org/blood/article-abstract/137/22/3027/475576/Dose-schedule-adjusted-Rd-R-vs-continuous-Rd-for?redirectedFrom=fulltext | https://doi.org/10.1182/blood.2020009507
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Descrizione: [Author Vsn] Larocca A et al. Blood. 2021 Jun 3;137(22):3027-3036. doi: 10.1182/blood.2020009507. PMID: 33739404. © 2021 by The American Society of Hematology. The published version is available at: https://ashpublications.org/blood/article-abstract/137/22/3027/475576/Dose-schedule-adjusted-Rd-R-vs-continuous-Rd-for?redirectedFrom=fulltext | https://doi.org/10.1182/blood.2020009507
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1790890
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