Efficacy of carfilzomib lenalidomide dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma according to risk status: Results from the FORTE trial.

Abstract

8002 Background: High and comparable rates of MRD negativity were seen in NDMM pts after 4 28-day induction cycles with KRd followed by ASCT and 4 KRd consolidation (KRd_ASCT_KRd) and after 12 KRd cycles (KRd12), showing the superiority of both regimens over KCd induction-ASCT-KCd consolidation (KCd-ASCT-KCd) (Gay F ASH 2018). Here we evaluated the benefit of KRd_ASCT_KRd vs KRd12 in specific subgroups of pts. Methods: 474 NDMM pts ≤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 R-ISS 1 and R-ISS 2/3. Since high-risk pts may sometimes respond rapidly, but then relapse early, we also analyzed the rate of early relapse (<18 months from randomization). We performed a multivariate logistic regression analysis to evaluate factors predictive of early relapse. Results: Median follow-up was 25 months. Rates of ≥VGPR, ≥CR, sCR, MRD negativity were comparable between KRd_ASCT_KRd and KRd12 overall, in pts with R-ISS Stage 1 and with R-ISS Stage 2/3 (Table). A significantly lower number of pts experienced early relapse with KRd_ASCT_KRd vs KRd12 (12 pts [8%] vs 26 pts [17%]; P=0.015). This difference was mainly related to a significantly lower rate of early relapse in R-ISS Stage 2/3 pts receiving KRd_ASCT_KRd vs KRd12 (11 pts [12%] vs 22 pts [23%]; P=0.05); no difference was seen in R-ISS 1 (0 vs 2 pts). In multivariate regression analysis, KRd_ASCT_KRd vs KRd12 reduced the risk of early progression (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 compared with R-ISS 1. Conclusions: KRd-ASCT-KRd and KRd12 were equally effective in inducing high-quality responses, with about 50% of high-risk pts achieving MRD negativity. In high-risk pts ASCT reduced the risk of early relapse. Clinical trial information: NCT02203643. [Table: see text]

Summary of the Third Annual Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling

“…Subsequently, Francesca Gay presented updated data from the FORTE trial during the 2019 American Society of Clinical Oncology national meeting [13]. Of particular interest were the premaintenance and 1-year persistent MRD negativity rates broken down by revised international staging system (R-ISS).…”

Development of a method for clinical pharmacokinetic testing to allow for targeted Melphalan dosing in multiple myeloma patients undergoing autologous transplant

“…There was a statistically significant difference between the mean AUC across the 6 groups based on the HDM and ASCT remains standard of care based on randomized trials demonstrating significant improvement in progression-free survival 1 and higher minimal residual disease negativity proportion when compared to induction therapy that did not involve transplant. 30 While it remains a standard of care in fit patients, efforts to improve efficacy to decrease the 20% of patients who relapse within 24 months 1 while decreasing toxicities (5% with significant mucositis despite cryotherapy and 10% with tachyarrhythmia) are needed.…”

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“…Длительная терапия леналидомидом также может стать препятствием для эффективного сбора аутологичных (ауто) ГСК. Современные программы терапии типа RVd или KRd позволяют сократить индукцию до 3-4 циклов [18,19].…”

“…Время после аутоТГСК, годы Наилучшие результаты у данного пациента с ММ высокого цитогенетического риска можно было получить с помощью наиболее активных индукционных режимов типа RVd или KRd. Схема RVd позволяет получить в результате индукции до 45 % охЧР и более глубоких ответов [18], KRd -74 % [19]. В первом исследовании после индукции и одной аутоТГСК частота ответов ≥ охЧР составила 77 %, включая 65 % случаев с МОБ-отрицательным статусом, во втором -89 и 58 % соответственно [18,19].…”