Autologous Transplantation Versus Cyclophosphamide-Lenalidomide-Prednisone Followed By Lenalidomide-Prednisone Versus Lenalidomide Maintenance in Multiple Myeloma: Long-Term Results of a Phase III Trial

Konference: 2015 57th ASH Annual Meeting - účast ČR

Kategorie: Mnohočetný myelom

Téma: 731. Clinical Autologous Transplantation: Results

Číslo abstraktu: 392

Autoři: Francesca Gay; MD Valeria Magarotto; MD Maria Teresa Petrucci; M.D. Francesco Di Raimondo; Doc.MUDr. Luděk Pour, Ph.D.; MD Tommaso Caravita; Prof.MUDr. Vlastimil Ščudla, CSc.; MD Anna Maria Cafro; Prof. MD Anna Marina Liberati; Stefano Spada; Doc. MUDr. Vladimír Maisnar, Ph.D.; Norbert Pescosta; Dr. Roberto Ria; M.D. Massimo Offidani; MD Sara Bringhen; Annalisa Bernardini; Francesca Patriarca; M.D. Paolo Corradini; Robert (Robin) Foa (Foà); MD Nicola Cascavilla; Lucio Catalano; MD Andrew Spencer; prof. MUDr. Roman Hájek, CSc.; MD Mario Boccadoro; MD Antonio P. Palumbo

Introduction. High-dose melphalan plus autologous stem-cell transplantation (ASCT) is the standard approach in newly diagnosed, transplant-eligible myeloma patients. We compared consolidation with high-dose melphalan plus ASCT versus cyclophosphamide–lenalidomide-dexamethasone (CRD), and maintenance with lenalidomide-prednisone (RP) versus lenalidomide alone (R).

Methods. This is an open-label, randomized, phase 3 study. We enrolled newly diagnosed, transplant-eligible myeloma patients aged ≤65 years. Using a 2-by-2 factorial design, we randomized patients to consolidation with melphalan 200 mg/m2 (MEL200) followed by ASCT or CRD (cyclophosphamide 300  mg/m2 days 1, 8, 15; dexamethasone 40 mg days 1, 8, 15, 22; lenalidomide 25 mg days 1–21); and to maintenance with RP (lenalidomide 10 mg days 1–21; prednisone 50 mg every other day) or R alone. The primary endpoint was progression-free survival (PFS).

Results. 389 patients were enrolled between July 6, 2009 and May 6, 2011. Median follow-up was 54.5 months. MEL200 significantly increased PFS (median PFS from the start of consolidation: 43.3 versus 28.6 months; HR 0.40, P<0.001) and overall survival (OS; 4‑year: 86% versus 73%; HR 0.42, P=0.004) compared with CRD. Median PFS from the start of maintenance was 37.5 months with RP versus 28.5 months with R maintenance (HR 0.84, P=0.336); 3-year OS was 83% with RP versus 88% with R maintenance (HR 1.53, P=0.210). Grade 3-4 hematologic toxicities (84% versus 26%, P<0.001), gastrointestinal toxicities (20% versus 5%, P<0.001) and infections (19% versus 6%, P=0.002) were higher with MEL200 than with CRD. No significant difference in adverse events (AEs) between RP and R was noticed. The most frequent grade 3-4 hematologic AEs were neutropenia (8% with RP versus 13% with R; P=0.193), infections (8% with RP versus 5% with R; P=0.417), systemic AEs (6% vs 2%; P=0.174) and vascular AEs (4% with RP versus 2% with R; P=0.449). In the RP arm, lenalidomide dose-reduction for AEs was required in 9% of patients; prednisone dose-reduction was required in 36% of patients (median time to prednisone dose-reduction: 4 months); 5% discontinued treatment for toxicity and 3% stopped treatment after developing a second primary malignancy (SPM). In the R arm, lenalidomide dose-reduction was required in 21% of patients; 8% discontinued lenalidomide for toxicity; 2% stopped treatment after developing a SPM. The median duration of lenalidomide treatment was comparable in the 2 groups.

Conclusions. MEL200 significantly prolonged PFS and OS compared with CRD, regardless of maintenance.  RP maintenance did not significantly improve PFS and OS compared with R alone.

Disclosures: Gay: Celgene: Honoraria , Membership on an entity’s Board of Directors or advisory committees ;Janssen-Cilag: Honoraria ; Sanofi: Membership on an entity’s Board of Directors or advisory committees . Off Label Use: Use off-label of drugs for the dose and/or schedule and/or association. Petrucci: Celgene: Honoraria ;Janssen-Cilag: Honoraria ; Sanofi: Honoraria ; Bristol-Myers Squibb: Honoraria . Di Raimondo: Janssen-Cilag, Celgene: Honoraria . Caravita: Celgene: Honoraria . Ria: Italfarmaco: Honoraria ; Novartis: Honoraria ; Janssen-Cilag: Honoraria ; Celgene: Honoraria . Offidani: Janssen-Cilag, Celgene, Sanofi, Amgen, Mundipharma: Honoraria . Bringhen: Merck Sharp & Dohme: Membership on an entity’s Board of Directors or advisory committees ;Janssen-Cilag, Celgene, Novartis: Honoraria ; Onyx: Consultancy . Patriarca: Janssen-Cilag, Celgene, Merck Sharp & Dohme: Honoraria . Spencer: Celgene: Honoraria . Hajek: Merck Sharp & Dohme: Consultancy , Honoraria ;Janssen-Cilag: Honoraria ; Celgene: Consultancy , Honoraria . Boccadoro: Sanofi: Consultancy , Membership on an entity’s Board of Directors or advisory committees ; Celgene: Consultancy , Membership on an entity’s Board of Directors or advisory committees ; Onyx Pharmaceuticals: Consultancy , Membership on an entity’s Board of Directors or advisory committees ; Janssen-Cilag: Consultancy , Membership on an entity’s Board of Directors or advisory committees . Palumbo: Novartis, Sanofi Aventis: Honoraria ; Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy , Honoraria .

http://www.hematology.org/

www.bloodjournal.org

Datum přednesení příspěvku: 6. 12. 2015