S872 CARFILZOMIB LENALIDOMIDE DEXAMETHASONE (KRD) WITH OR WITHOUT TRANSPLANTATION IN NEWLY DIAGNOSED MYELOMA (FORTE TRIAL): EFFICACY ACCORDING TO RISK STATUS
Authors: F. Gay, C. Cerrato, D. Rota Scalabrini, A. Belotti, M. Galli, E. Zamagni, M. Offidani, P. Omedé, F. Monaco, P. Tosi, O. Annibali, F. Pisani, R. Troia, A. Pascarella, F. Ferrara, M. Cea, B. Dalla Palma, F. Patriarca, S. Aquino, A. Palmas, A. Siniscalchi, M. Grasso, A. Palumbo, A. Ledda, P. Musto, M. Cavo, M. Boccadoro
Journal: HemaSphere (2019)

Background: High and comparable rates of response and minimal residual disease (MRD) negativity were reported with four 28‐day induction cycles of KRd followed by autologous stem‐cell transplantation (ASCT) and 4 KRd consolidation (KRd_ASCT_KRd), and with 12 KRd cycles (KRd12) in newly diagnosed myeloma (NDMM) patients. Of note, both regimens were superior to carfilzomib‐cyclophosphamide‐dexamethasone (KCd) induction followed by ASCT and KCd consolidation (KCd‐ASCT‐KCd) (Gay F ASH 2018). Aims: We evaluated the benefit of KRd_ASCT_KRd vs KRd12 in specific subgroups of patients according to their risk status. Methods: 474 NDMM patients ≤65 years were randomized to KRd_ASCT_KRd or KRd12 or KCd_ASCT_KCd. We compared rate of ≥VGPR, ≥CR, sCR, MRD negativity (centralized, second generation flow cytometry, sensitivity 10 −5 ) after consolidation with KRd_ASCT_KRd vs KRd12 in patients with available Revised International Staging System (R‐ISS) 1 and R‐ISS 2/3. High‐risk patients may sometimes respond rapidly, but subsequently relapse early. Therefore, we also analyzed the rate of early relapse (&lt;18 months from randomization) in the two arms. We performed a multivariate logistic regression analysis to evaluate factors predictive of early relapse. Results: Median follow‐up was 25 months. On intention‐to‐treat analysis, KRd_ASCT_KRd and KRd12 showed similar rates of ≥VGPR, ≥CR, sCR, MRD negativity in the overall population (Table 1A). Similarly, MRD negativity and response rates in the two treatment arms were comparable in the subgroups of patients with R‐ISS Stage 1 and with R‐ISS Stage 2/3 (Table 1B). Of note, rate of MRD negativity in high‐risk patients was around 50% (Table 1B). In the overall population, early relapses were significantly lower with KRd_ASCT_KRd vs KRd12 (12 patients [8%] vs 26 patients [17%]; P = 0.015), mainly related to a significantly lower rate of early relapse in patients with high risk status (R‐ISS Stage 2/3) (11 patients [12%] vs 22 patients [23%]; P = 0.05, respectively). Very few patients with R‐ISS Stage 1 relapsed, with no difference between KRd_ASCT_KRd and KRd12 (0 vs 2 patients). In multivariate regression analysis, patients receiving KRd_ASCT_KRd had a reduced risk of early relapse compared with those treated with KRd12 (OR 0.42; P = 0.021); R‐ISS Stage 2 (OR 3.6; P = 0.001) and R‐ISS Stage 3 (OR 4.85; P = 0.003) increased the risk of early relapse compared with R‐ISS 1. Summary/Conclusion: KRd‐ASCT‐KRd and KRd12 were equally effective in inducing high‐quality responses, and approximately 50% of high‐risk patients achieved MRD negativity. In addition, ASCT proved to be beneficial in high‐risk patients, reducing the risk of early relapse. image