Continuous treatment (CT) versus fixed duration of therapy (FDT) in newly diagnosed myeloma patients: PFS1, PFS2, OS endpoints.

8515 Background: Continuous therapy significantly prolongs remission duration, resistant relapse may reduce the duration of subsequent remission which can negatively impact on OS. PFS1 defines the time from start of therapy to the occurrence of 1st relapse. PFS2 is defined as per EMA as the time from start of therapy to the occurrence of 2nd relapse, incorporating the duration of both 1st and 2nd remission. We evaluated PFS1, PFS2 and OS in newly diagnosed multiple myeloma (NDMM) patients who received CT or FDT. Methods: Patients were enrolled in 2 phase III randomized trials, comparing CT vs FDT (RVMM209: lenalidomide-based induction, consolidation, followed by maintenance CT vs lenalidomide-based induction, consolidation, no maintenance FDT; GIMEMA0305: bortezomib-based induction followed by maintenance (CT) vs bortezomib-based induction, no maintenance FDT). At diagnosis, in all randomized patients, we evaluated PFS1 (time: diagnosis followed by 1st relapse), PFS2 (time: diagnosis followed by 2nd relapse), and OS (time: diagnosis followed by death). In patients who experienced 1st relapse we tested 2nd PFS (time: 1st relapse followed by 2nd relapse) and survival from relapse (time: 1st relapse followed by death). Results: In the pooled analysis, 452 patients received CT and 461 patients received FDT. Median follow-up was 52 months mo. CT significantly prolonged PFS1 (median 35 vs 24 mo, HR 0.58; P<0.0001), PFS2 (median 63 vs 47 mo, HR 0.69, p=0.0001) and OS (median not reached NR vs 70 mo, HR 0.70, P=0.0019) in comparison with FDT. 2nd PFS and OS from relapse were similar among patients who received CT or FDT upfront. Results were similar in the single studies (Table). Conclusions: In NDMM patients, CT significantly improved PFS1, PFS2, and OS. Prolongation of PFS2 suggests that the clinical benefit observed during 1st remission is not cancelled by a shorter 2nd remission. PFS2 should be included in all CT vs FDT studies to evaluate the risk of tumor-resistance induced by CT. Clinical trial information: NCT01063179 and NCT00551928. GIMEMA MM0305 RVMM209 CT FDT HR P CT FDT HR P (Median, mo) (Median, mo) From diagnosis PFS1 35 24 0.58 <0.001 38 25 0.58 <0.001 PFS2 59 42 0.69 0.003 63 49 0.69 0.015 OS NR 60 0.70 0.01 NR NR 0.68 0.047 From 1st relapse PFS 14 12 1.1 0.61 17 19 1.09 0.61 OS 26 28 0.99 0.94 47 42 1.0 0.99