Introduction: Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to compare the efficacy of relevant therapies for the treatment of TIE patients with NDMM. Methods: Progression-free survival (PFS) and overall survival (OS) from large randomised controlled trials (RCTs) evaluating different treatment options for TIE patients with NDMM were compared in a network meta-analysis (NMA). The NMA includes recent primary and long-term OS readouts from SWOG S0777, ENDURANCE, MAIA, and ALCYONE. Relevant trials were identified through a systematic literature review. Relative efficacy measures (i.e., hazard ratios [HRs] for PFS and OS) were extracted and synthesised in random-effects NMAs. Results: A total of 122 publications describing 45 unique RCTs was identified. Continuous lenalidomide/dexamethasone (Rd) was selected as the referent comparator. Daratumumabcontaining treatments (daratumumab/lenalidomide/dexamethasone [D-Rd], daratumumab/ bortezomib/melphalan/prednisone [D-VMP]) and bortezomib/lenalidomide/dexamethasone (VRd) had the highest probabilities of being
e19512 Background: Acute myeloid leukemia (AML) is an orphan disease with one of the lowest five-year survival rates among myeloid malignancies. Recently, a randomized, open label study among previously untreated, chemotherapy-ineligible AML patients demonstrated improved overall survival (OS) among patients treated with glasdegib (GLAS) + LDAC compared with LDAC alone. Two trials of AZA vs. conventional care regimens report data by bone marrow blast (BMB) counts: one with 20-30% and the other with >30%. In the absence of head-to-head comparisons, this study aims to perform the indirect treatment comparison between GLAS+LDAC and AZA by BMB counts. Methods: As there were potential imbalances between the GLAS and AZA trials and within the AZA trial arms in the baseline characteristics (e.g. poor cytogenetics% and de novo%), simulated treatment comparisons (STCs) for GLAS+LDAC vs. LDAC were performed to derive robust estimation by adjusting for the imbalances in the baseline effect modifiers. Afterwards, the classical network meta-analysis (NMA) was conducted. To derive the hazard ratio (HR) of GLAS+LDAC vs. AZA, three NMAs were conducted in each BMB group. Each NMA used a different HR of GLAS+LDAC vs. LDAC: 1) an unadjusted HR (classical NMA), 2) an STC adjusted HR adjusting for potential imbalances between the trials, and 3) an STC adjusted HR additionally accounting for potential imbalances between arms within the AZA trial. Results: In the 20-30% BMB group (N = 30), the OS HRs of GLAS+LDAC vs. AZA resulting from the three respective NMAs were as follows: 1) 0.46 [95% confidence interval: 0.10-2.14], 2) 0.31 [0.06-1.69], and 3) 0.36 [0.06-2.15]. In the > 30% BMB group (N = 80), the HRs were 1) 0.69 [0.39-1.20], 2) 0.48 [0.23-0.97], and 3) 0.48 [0.24-1.00]. All the HRs suggest that patients with GLAS+LDAC have a survival advantage over patients with AZA. Conclusions: Both the classical NMAs and the NMAs based on the STC adjusted HRs correcting for the potential imbalances at baseline suggest that GLAS+LDAC may be preferred over AZA as a treatment option for previously untreated chemotherapy-ineligible AML patients regardless of BMB counts. [Table: see text]
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