Kategorie: Mnohočetný myelom
Téma: Multiple myeloma - Translational and clinical studies
Číslo abstraktu: P221
Autoři: Francesca Gay; MD Sara Bringhen; M.D. Massimo Offidani; Prof. MD Anna Marina Liberati; Claudia Cellini; MD Valeria Magarotto; Giulia Benevolo; Gabriele Aitoro; Francesca Patriarca; Paola Omede; Concetta Conticello; MD Vittorio Montefusco; M.D. Davide Rossi; Carmela Palladino; Doc.MUDr. Luděk Pour, Ph.D.; Alessandro Allegra; Giuseppe Pietrantuono; M.D. Antonietta Pia Falcone; Alberto Rocci; Renato Zambello; Antonio Ledda; Silvia Gentili; MD Pellegrino Musto; MD Mario Boccadoro; prof. MUDr. Roman Hájek, CSc.; MD Antonio P. Palumbo
Lenalidomide plus low-dose dexamethasone (Rd) and melphalan- prednisone-lenalidomide (MPR) followed by lenalidomide maintenance showed to be effective and safe in elderly newly diagnosed multiple myeloma(MM) patients (pts). Cyclophosphamide represents a valid alkylant alternative in combination with steroids and novel agents. No formal comparison between these combinations has been performed until now.
To assess the efficacy and safety of the lenalidomide plus low dose dexamethasone (Rd) vs Melphalan-Prednisone-Lenalidomide (MPR) and Cyclophosphamide-Prednisone-Lenalidomide (CPR) in a community-based setting of MM pts ≥65 years old or not eligible to autologous stem cell transplantation.
Pts with symptomatic MM were randomized (1:1:1) to receive 9 28- day cycles of Rd, MPR or CPR. Upfront dose reductions of dexamethasone, melphalan and cyclophosphamide were performed, according to pt age (Rd: lenalidomide 25 mg/day for 21 days; dexamethasone 40 mg on days1, 8, 15 and 22 in pts 65-75 years old and 20 mg in those >75 years; MPR: lenalidomide 10 mg/day for 21 days; melphalan orally 0.18 mg/Kg for 4 days in pts 65-75 years old and 0.13 mg/Kg in >75 years pts; prednisone 1.5 mg/Kg for 4 days; CPR: lenalidomide 25 mg/day for 21 days; cyclophosphamide orally 50 mg/day for 21 days in pts 65-75 years old and 50 mg every other day (eod) in >75 years pts; prednisone 25 mg eod). After induction, pts were randomized to receive maintenance with lenalidomide (10 mg/day on day 1-21 every 28) alone or in combination with prednisone (25 mg eod), until disease progression. The primary endpoint was progression-free survival (PFS).
Between October 2009 and October 2012, 663 pts were enrolled (Rd:222, MPR:218; CPR: 223). Patient characteristics were well balanced in the three groups. Median age was 73 years in each arm; 37%, 40% and 36% of pts respectively in Rd, MPR and CPR arms were >75 years. Frail pts were 65% in the Rd arm, 65% in the MPR arm and 56% in CPR arm. (Table). At data cut-off all pts had completed the 9 induction cycles. Median follow-up was 19 months. Partial response (PR) rate was similar in the 3 arms: 74%, 74% and 75% respectively in Rd, MPR and CPR group, including 35% very good partial response in Rd, 29% in MPR and 26% in CPR. A trend towards a higher complete response (CR) rate was noticed in the MPR group (12%), similar CR rate was reported in Rd (5%) and CPR (7%). At least 1 grade ≥3 hematological adverse event (AE) was reported in 28% Rd pts, 62% MPR pts and 29% CPR pts. The main hematological AE was neutropenia (Rd: 24%; MPR: 59%; CPR: 26%). At least 1 grade ≥3 non-hematological AE was observed in 25% of Rd pts, 29% of MPR pts and 22% of CPR pts. The most common grade ≥3 non-hematological AEs were infections (Rd: 6%, MPR: 9%, CPR:4%) and dermatological toxicities (Rd: 4%, MPR: 4%, CPR: 7%). Treatment discontinuations for toxicity were 7% in Rd, 12% in MPR and 12% in CPR. The main reason for treatment discontinuation was non-hematological toxicity in Rd (6%) and CPR (11%). Only 1% of pts stopped treatment for hematological AEs in Rd and CPR. In the MPR arm 7% of pts stopped treatment for hematological AEs and 5% for non-hematological AEs. Rate of toxic deaths was similar in the 3 arms (4% Rd, 4% MPR and 5% CPR).
Datum přednesení příspěvku: 14. 6. 2013