LENALIDOMIDE-DEXAMETHSONE (RD) VS MELPHALAN-LENALIDOMIDE-PREDNISONE (MPR) VS CYCLOPHOSPHAMIDE-PREDNISONE-LENALIDOMIDE (CPR) IN ELDERLY COMMUNITY-BASED NEWLY DIAGNOSED MYELOMA PATIENTS

ABSSUB-3980

Background: Rd and MPR showed to be effective and safe in newly diagnosed multiple myeloma (MM) patients. Cyclophosphamide is a less toxic alkylating alternative agent. A formal comparison between 2-drug and 3-drug lenalidomide-containing combinations has not yet been performed.

Aims: To compare a not-alkylating regimen (Rd) vs two different alkylating-based regimens (MPR or CPR) in a community-based setting of MM pts ≥65 years old or not eligible for autologous stem cell transplantation. The primary endpoint was progression-free survival (PFS).

Methods: 662 patients with newly diagnosed MM were randomized to receive nine 28-day cycles of Rd, MPR or CPR. Upfront dose reductions of dexamethasone, melphalan and cyclophosphamide were performed according to patients age (Rd: lenalidomide 25 mg/day for 21 days; dexamethasone 40 mg on days 1,8,15 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 in >75 years pts; prednisone 25 mg every other day). After induction, patients were randomized to receive maintenance with lenalidomide alone (R) or with prednisone (RP), until disease progression.

Results: Patients characteristics were well balanced in all groups. 212 patients in Rd, 210 in MPR and 220 in CPR arm were evaluable for response. After induction, at least partial response (PR) rate was 78%, 73% and 73% in Rd, MPR and CPR arms, respectively (Rd vs MPR p=0.138; Rd vs CPR p=0.205). After a median follow-up of 26 months, median PFS was 22 months in Rd, 27 months in MPR and 23 months in CPR patients (Rd vs MPR p=0.231; Rd vs CPR p= 0.862). Grade ≥ 3 hematologic adverse events were 29% in Rd, 67% in MPR and 32% in CPR arms (Rd vs MPR p<0.0001; CPR vs MPR p<0.0001 ). No difference was noticed in grade ≥ 3 non-hematologic adverse events between the treatment groups: 29% with Rd, 31% with MPR, 30% with CPR. 203 patients in the R group and 198 in the RP group started maintenance treatment. After a median follow-up of 18 months, 2-year PFS from the beginning of maintenance treatment was 52% in R and 58% in RP patients (p=0.570). A sub-group analysis according to patient’s frailty, as established by ADL, IADL, Charlson scores and age (Larocca A, et al. Blood ASH meeting 2013; 122: abstract 687) was conducted. No significant PFS difference was reported among the three arms in fit and frail patients. Grade ≥ 3 hematologic toxicity was sensibly higher in the MPR arm in both fit and frail patients.

Summary/Conclusion: In a community-based population, triplet alkylating combinations do not offer a significant PFS advantage over doublet therapy without alkylating agents. In a subgroup analysis according patient’s frailty, PFS was similar in fit, unfit and frail patients regardless of treatment, yet grade ≥ 3 hematologic toxicity was higher with MPR. Updated data will be presented at the meeting.

Keywords: Elderly, Imids, Melphalan, Multiple myeloma

http://www.ehaweb.org/