PF637 EFFICACY OF LENALIDOMIDE AND LOW‐DOSE DEXAMETHASONE IN NEWLY DIAGNOSED PATIENTS WITH MULTIPLE MYELOMA: RESULTS FROM A META‐ANALYSIS OF RANDOMIZED CONTROLLED TRIAL EVIDENCE

Background: Lenalidomide and low‐dose dexamethasone (Rd) is an established treatment option for patients with newly diagnosed multiple myeloma (NDMM) who are not candidates for autologous stem cell transplantation (ASCT). The efficacy and safety of Rd was demonstrated in the FIRST trial, which showed a significant improvement in overall survival (OS) with Rd compared with combination melphalan, prednisone, and thalidomide. The alkylator‐free Rd regimen is now a recommended treatment option in the European Society for Medical Oncology (ESMO) guidelines (Moreau et al. Ann Oncol. 2017;28:iv52–61). Recent trials comparing Rd + bortezomib or Rd + daratumumab with Rd have contributed to the growing body of evidence regarding the efficacy of Rd in patients with NDMM. Aims: To obtain a consolidated median estimate for OS and progression‐free survival (PFS) outcomes from phase 3 registration studies in NDMM patients not intended for ASCT receiving Rd. Methods: Details of trial characteristics, baseline patient characteristics, and outcomes were extracted from phase 3 registration studies of NDMM patients treated with Rd. Kaplan–Meier curves for OS and PFS were digitized and patient‐level data were estimated numerically. These estimated patient‐level data were then pooled in a Bayesian meta‐analysis. Weibull, Gompertz, and second‐order fractional polynomial models were fit to the data to estimate the survival function. Results: In this meta‐analysis of randomized controlled trials, there was some variance among the three trials, regarding inclusion criteria and baseline characteristics. Notably, SWOG S0777 enrolled patients who were not intended for immediate ASCT, whereas FIRST and MAIA enrolled patients who were ineligible for ASCT. Median follow‐up for MAIA was shorter than FIRST or SWOG S0777 (28 months vs 67 and 84 months, respectively). As this precluded the stable estimation of heterogeneity, a fixed‐effects model was employed. Using the best‐fitting models, the median OS with Rd was estimated to be 67.2 months (95% confidence interval [CI] 61.3–74.2 months) and the median PFS was estimated to be 28.9 months (95% CI 26.8–31.3 months). Estimated results were consistent with the results from the individual trials (median PFS values for FIRST, S0777, and MAIA were 26.0, 30, and 31.9 months, respectively; median OS was 59.1, 64, and not reported, respectively) and subgroups tested (where data were available). The adverse events reported with Rd across these 3 trials were consistent with the known safety profile for this regimen. Summary/Conclusion: This analysis demonstrated a consistent treatment benefit for Rd across the phase 3 trials studied, with estimates for median OS and PFS exceeding 5 years and 2 years respectively, in patients with NDMM ineligible for ASCT. The results support the ESMO guideline recommendation for Rd as a first‐line standard of care in this setting and its role in the development of novel combination regimens.