Kategorie: Mnohočetný myelom
Téma: Myeloma and other monoclonal gammopathies - Clinical
Číslo abstraktu: S1335
Autoři: Francesca Gay; M.D. Federica Cavallo; M.D. Francesco Di Raimondo; Izhar Hardan; MD Arnon Nagler, MSc.; M.D. Paolo Corradini; prof. MUDr. Roman Hájek, CSc.; MD Maria Teresa Petrucci; MD Sara Pezzati; MD Michel Delforge, PhD; Francesca Patriarca; Francesca Donato; MD Lucia Pantani; Chiara (Clara) Nozzoli; Zhinuan Yu, PhD; Luana Boccadifuoco; MD Tommaso Caravita; Christian J. Jacques; Giulia Benevolo; Meletios Athanasios Dimopoulos, MD; Tommasina Guglielmelli; Dott.ssa Iolanda Donatella Vincelli; MD Giovannino Ciccone, PhD; MD Pellegrino Musto; MD Mario Boccadoro; MD Antonio P. Palumbo
Background: Continuous therapy significantly prolongs remission duration, but chemo-resistant relapse may reduce the duration of subsequent remissions, with negative impact on OS. In such situations, OS rather than PFS is the preferable endpoint. However, this is often deemed not feasible, thus endpoints such as PFS2 should be of importance (EMA guideline). PFS1 defines the time from randomization until the occurrence of 1st relapse. PFS2 defines the time from randomization until the occurrence of 2nd relapse, and incorporates the duration of both 1st and 2nd remissions.
Aims: To compare PFS1, PFS2 and OS in newly diagnosed multiple myeloma (NDMM) patients who received continuous treatment (CT) or fixed duration of therapy (FDT) upfront.
Methods: We included patients enrolled in 3 phase III randomized trials, comparing CT vs. FDT upfront (GIMEMA RV-MM-209: lenalidomide-based induction, consolidation, followed by maintenance [CT] vs lenalidomide-based induction, consolidation, no maintenance [FDT]; GIMEMA 0305: bortezomib-based induction followed by maintenance (CT) vs. bortezomib-based induction, no maintenance [FDT]; MM-015: lenalidomide-based induction, followed by maintenance [CT] vs. lenalidomide-based induction/melphalan-prednisone, no maintenance [FDT]). The analysis was performed on the intention-to-treat population. We evaluated PFS1 (time from randomization at diagnosis to 1st relapse), PFS2 (time from randomization at diagnosis to 2nd relapse), and OS (time from randomization at diagnosis to death) through a stratified analysis by protocol. At 1st relapse we tested 2nd PFS (time from 1st relapse to 2nd relapse) and survival from relapse (time from 1st relapse to death).
Results: In the pooled analysis, 604 patients were randomized to CT and 768 patients to FDT. The median follow-up for survivors was 48 months. CT significantly prolonged PFS1 (median 34 vs. 19 months, HR=0.52, 95% CI: 0.45-0.60, P<0.001), PFS2 (median 54 vs 38 months, HR=0.70, 95% CI: 0.61-0.82, p<0.001) and OS (median OS not reached vs. 60 months, HR=0.78, 95% CI: 0.65-0.93, P=0.006) in comparison with FDT (Figure). 392 patients who received CT upfront experienced 1st relapse in comparison with 626 patients who received FDT upfront. No differences in 2nd PFS and OS from relapse between patients who received CT or FDT upfront was noticed. Results were similar when the source studies were analyzed separately.
Summary/Conclusion: 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 very short 2nd remission. PFS2 should be included in all future trials to evaluate the impact of chemo-resistant relapse.
Keywords: Diagnosis, Maintenance, Multiple myeloma, Survival
Datum přednesení příspěvku: 15. 6. 2014