ALBERT

Description: Introduction: Achievement of MRD negativity in MM is associated with prolonged progression-free survival (PFS) and is being investigated as a potential surrogate for established clinical endpoints, such as PFS and overall survival (OS). Here, we evaluated the predictive utility of MRD in patients (pts) with MM for PFS and OS using a systematic literature review (SLR) and meta-analysis, and investigated how hazard ratios (HR) for PFS and OS, stratified by MRD status, changed for various pt subgroups. Methods: A SLR was conducted to identify all studies in MM reporting survival outcomes by MRD status (through 8 June 2019). In these studies, MRD was assessed by various assays (multiparametric flow cytometry [MFC], next generation sequencing [NGS], and polymerase chain reaction [PCR]), sensitivity thresholds (10-4, 10-5, and 10-6), and disease settings (relapsed/refractory MM [RRMM], transplant-eligible [TE] and transplant-ineligible [TIE] newly diagnosed MM [NDMM]). Studies with allogeneic transplant, where MRD was measured in peripheral blood or using PET-CT, or from which PFS and OS data could not be extracted were excluded from the analysis. To obtain a pooled effect estimate of MRD status on PFS and OS HRs, a meta-analysis was performed. Subgroup analyses were performed to adjust for variables expected to impact the association of MRD and PFS/OS outcomes. Variables were selected based on available qualitative evidence from studies. Statistical analyses were performed using the 'metafor' R package for meta-analyses. Results: 143 publications met the inclusion criteria; 86 publications were included in the meta-analysis based on data availability (65 PFS and 28 OS HRs). Outcomes for PFS (N = 8590) and OS (N = 3392) were significantly improved for MRD-negative pts: PFS HR 0.35 (95% confidence interval [CI], 0.31-0.39) and OS HR 0.48 (95% CI, 0.41-0.55; P

Description: INTRODUCTION: The recent FENOC comparative trial (Astermark et al. 2007) reported comparable efficacy for rFVIIa and APCC in the treatment of joint bleeds in patients with hemophilia complicated by inhibitors. A systematic review was combined with a Bayesian meta-regression analysis to place the FENOC results within the context of earlier non-comparative studies and to identify key variables influencing treatment efficacy. METHODS: A systematic literature search was performed using electronic databases, web based trial registers, and grey literature. Clinical studies and/or trials in hemophilia patients with inhibitors receiving on-demand treatment with rFVIIa or APCC were included. Outcome of interest was the time of successfully stopping joint bleeds taking explicit account of repeated dosing. To model the latter, the regression model included a repeating Gompertz hazard function to compare the efficacy of standard rFVIIa treatment (one 90 μg/kg rFVIIa infusion every 3 hrs) with standard APCC treatment (one 75 IU/kg APCC infusion every 12 hrs). The hazard function (the conditional probability of ending the bleeding) was characterized by a repeated pattern of fixed increases after each infusion and by subsequent decreases thereafter. It was assumed that each sequential infusion had the same effect on the hazard resulting in a shark tooth like function. Covariates included were medication type, medication type combined with dosage (measured in μg/kg for rFVIIa and IU/kg for APCC), efficacy rating scale method, and efficacy rater. RESULTS: Of the 17 studies included in the systematic review, 14 provided adequate data to be included in the Bayesian model, reporting on almost 2,000 joint bleeds combined (of which 96 were from the FENOC itself). The analysis demonstrated that medication type combined with dosage appears to have a statistically significant effect on efficacy of treatment. For rFVIIa the model estimated that 75%, 94%, and 98% of bleeds would be treated effectively after 12, 24, and 36 hours respectively. In contrast, for APCC the model estimated that 39%, 63%, and 78% of bleeds would be treated effectively after 12, 24 and 36 hours respectively. CONCLUSIONS: The FENOC study demonstrated similar efficacy levels for treatment with rFVIIa and APCC. In contrast, the present meta-analysis including 14 studies and almost 2,000 joint bleeds estimated that standard treatment with rFVIIa is likely to result in higher efficacy levels at the 12, 24 and 36 hour time points than treatment with APCC. This implies that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than APCC.

Description: Background: In clinical trials of second line and later line therapies for chronic myeloid leukemia (CML), to date only single arm trials have been conducted for the available treatments (i.e. Bosutinib, Dasatinib, Nilotinib and Ponatinib). These trials included heterogeneous patient populations in terms of line of treatment, stage of disease and other patient- and disease baseline characteristics that may impact the outcomes of the treatment. This hampers any direct or indirect comparisons of these second line CML treatments in terms of efficacy measures such as progression-free survival (PFS) and overall survival (OS). In this situation (i.e. lack of common comparator), matching-adjusted indirect treatment comparisons (MAICs) can be applied. Objective: The aim of this research was to compare the efficacy (PFS and OS) of Bosutinib, Dasatinib, Nilotinib and Ponatinib in second line chronic phase CML patients by means of MAICs. Patient data are reweighted such that their medians on demographic and clinical characteristics match those of the aggregated comparator trial, in order to adjust for cross-trial differences in those baseline characteristics. Outcomes of the reweighted patient level dataset are then compared with those of the aggregated comparator trial. Methods: A systematic literature review of second-line or later CML Phase II and Phase III clinical trials identified 2 trials for Bosutinib, 11 trials for Dasatinib, 8 trials for Nilotinib and 2 trials for Ponatinib. For the MAIC, only second line chronic phase trials with three or more years of follow-up (to allow for sufficient differentiation of treatments over time) were considered, resulting in 1 trial for Bosutinib (NCT00261846), 1 trial for Dasatinib (CA180-034), 1 trial for Nilotinib (NCT00109707) and no trials for Ponatinib. To adjust for cross-trial differences, patient data from the Bosutinib trial were subject to the inclusion and exclusion criteria reported in the comparator trials, and were weighted to match all available summary baseline characteristics reported in the 1 Dasatinib trial and the 1 Nilotinib trial. The baseline characteristics considered for reweighing were as follows: age, gender, Imatinib resistant/intolerant, disease duration, and prior stem cell transplantation. After the MAICs, PFS and OS were compared based on hazard ratios (HR) derived by Cox proportional hazard (PH) regressions using the reweighed Bosutinib dataset. The Cox PH assumption was tested with log cumulative hazard plots, Schoenfeld residuals and its corresponding statistical test. In case the PH assumption did not hold, Cox regressions with time varying coefficients were tested and the relative restricted mean survival time (RMST) was estimated. Results: Comparing Bosutinib to Nilotinib resulted in HRs for PFS and OS of 2.0 (

Description: Introduction : Daratumumab (DARA) is a human CD38 antibody approved in combination with standard-of-care (SoC) regimens in pts with NDMM who are TIE. DARA-based treatments showed significantly improved progression-free survival (PFS) in pts with TIE NDMM in ongoing phase 3 studies ALCYONE (DARA + bortezomib/melphalan/prednisone [D-VMP] vs VMP) and MAIA (DARA + lenalidomide/dexamethasone [D-Rd] vs Rd continuous). An NMA allows estimation of the relative efficacy of regimens not compared in head-to-head trials. A previous NMA examined D-VMP and D-Rd vs comparators (Facon T et al., EHA 2019), excluding the SWOG S0777 study (bortezomib/lenalidomide/dexamethasone [VRd]; Durie BG, et al. Lancet 2017) as it enrolled both transplant-eligible (TE) and TIE pts, and data for pts who are TIE only (~50% [aged ≥65 y and frail]) were unavailable. In this NMA, D-Rd and D-VMP had the highest probabilities of being more effective than reference treatment Rd continuous in terms of PFS. Recently, VRd received EMA approval for treatment of TIE NDMM based on SWOG S0777, but results specific to TIE pts are still unavailable. Recent NMAs of TIE pts (Blommestein HM et al., Haematologica, 2019; Weisel et al., EHA 2019; Cao Y et al., Clin Lymphoma Myeloma Leuk, 2019) have included data from the the intent-to-treat (ITT) population of SWOG S0777, though its inclusion violates the similarity assumption. Here, we present a sensitivity analysis of the previously-conducted NMA including all pts who received VRd in SWOG S0777 for a comprehensive view of the comparative effectiveness of DARA-based treatments in TIE NDMM. Methods: VRd was included as part of a sensitivity analysis of the previous NMA based on the ITT population, reporting PFS and overall survival (OS). The Guyot method was used to estimate OS hazard ratios (HRs) for pts aged ≥65 y (proxy for TIE) from SWOG S0777 (Durie BG et al., ASH 2018). Median follow-up in ALCYONE and MAIA was 27.8 months and 28.0 months, respectively. Based on a systematic literature review conducted through January 2019, both PFS and OS were extracted and synthesized in Bayesian NMAs. Choice of fixed- or random-effects (FE or RE) model was based on lowest deviance information criterion (DIC) and/or presence of heterogeneity in the network. Rd continuous was selected as reference, as it was commonly included in guidelines across regions. For PFS and OS, HR

Description: Introduction: Standard-of-care (SoC) frontline treatments in Latin America (LATAM) for patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible include bortezomib- and thalidomide-based regimens. The uptake of novel MM therapies has been slow in the past decade in LATAM. Recently, the phase 3 ALCYONE study demonstrated that D-VMP significantly improved progression-free survival (PFS) and led to higher rates of deeper responses compared with bortezomib, melphalan, and prednisone (VMP) therapy alone for patients with NDMM who were transplant ineligible (Mateos MV, et al. NEJM. 2018;378[6]:518-528). In this propensity score matching (PSM) analysis, we compared the efficacy of D-VMP with SoC regimens used in LATAM in patients with NDMM who were transplant ineligible. Methods: Data for the D-VMP cohort were from the randomized, multicenter, open-label, international, phase 3 ALCYONE study, which enrolled patients from 162 sites in 25 countries between February 9, 2015 and July 14, 2016. Patients (N = 706) were randomly assigned to receive 9 cycles of VMP alone (n = 356) or with daratumumab until disease progression (D-VMP; n = 350). Data for the LATAM SoC cohort were from the retrospective, observational Hemato-Oncology Latin America (HOLA) study of patients with selected hematologic malignancies seen in 30 sites across 7 countries in LATAM from January 1, 2008 to December 31, 2015. Patients were required to be ≥18 years of age at MM diagnosis, to have follow-up data for ≥1 year following diagnosis or until death, and to have never received autologous stem-cell transplantation (ASCT). Follow-up continued until the patient's death or December 31, 2016, whichever occurred first. PSM was conducted to adjust for differences in baseline characteristics between the ALCYONE study and the HOLA registry. Several matching algorithms were tested (eg, exact, optimal, and nearest neighbor). The matching method with the lowest average standardized difference was used for further analyses. Considered baseline characteristics included median age (71 vs 64 years), male sex (46% vs 50%), International Staging System (ISS) I-III (20%, 40%, and 41% vs 11%, 19%, 35% and NA=34%), chronic kidney disease (CKD) (1% vs 33%), and hypercalcemia (11% vs 20%). Outcomes of interest were overall survival (OS) and PFS. OS and PFS were compared based on Cox hazard models. The following outcome regressions were conducted: naïve and multivariate regression on matched samples. The latter was the base case, as differences in baseline characteristics might persist after matching. Results: A total of 350 patients from the D-VMP ALCYONE cohort and 729 patients from LATAM in the HOLA cohort were considered for analysis. All D-VMP patients were included; among the HOLA cohort, 478 patients were not missing data for baseline characteristics and were included in the analysis of OS and PFS. The chi-square test showed that baseline characteristics were significantly different between the cohorts. The nearest neighbour PSM with caliper 0.05 was selected for OS and PFS. After matching, the chi-square test demonstrated that baseline characteristics of remaining matched patients were well-balanced (no significant differences in covariates) between D-VMP (n = 207) and HOLA (n = 207) in terms of median age (70 vs 70 years), sex (male, 50% vs 47%), ISS I-III (16%, 38%, and 46% vs 22%, 38%, and 40%), CKD (2% vs 3%), and hypercalcemia (16% vs 14%). D-VMP showed statistically significantly better OS and PFS compared with HOLA. The naïve hazard ratio for OS was 0.46 (95% CI: 0.34-0.61) and for PFS was 0.41 (95% CI: 0.34-0.50); the base case hazard ratio for OS was 0.48 (95% CI: 0.32-0.73) and for PFS was 0.44 (95% CI: 0.33-0.58; Figure). Conclusions: This analysis demonstrated a benefit of D-VMP over SoC treatments in LATAM for OS and PFS. Results should be considered in the context that ALCYONE OS data are immature, and there are potential limitations of temporal bias, measurement bias, and bias due to unobserved confounding factors between the two cohorts. Disclosures Hungria: BMS: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Martinez-Banos:Celgene, Amgen: Other: Advisory Board. Mateos:GSK: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; EDO: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dimopoulos:Sanofi Oncology: Research Funding. Cavo:Celgene, Janssen, Amgen, BMS, Abbvie, Takeda: Honoraria; Janssen, Celgene: Other: Travel Accommodations; Janssen, Celgene: Speakers Bureau; Janssen, Celgene, Amgen, Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Heeg:Ingress-Health: Employment. Lam:Janssen: Employment, Equity Ownership. Machnicki:Janssen: Employment, Equity Ownership. He:Janssen: Employment, Equity Ownership. Fernandez:Janssen: Employment, Equity Ownership.

Description: I ntroduction Acute myeloid leukemia (AML) is an orphan disease and has one of the lowest five-year survival rates among myeloid malignancies in United States (US) adults (28.3% on average, 5% of which are aged 65 years or older). Older patients with AML have few treatment options and are often not candidates for intensive induction chemotherapy, therefore novel therapeutic strategies are needed. A phase II randomized study (Cortes et al. 2019) among newly diagnosed AML patients who were not candidates for intensive induction chemotherapy demonstrated improved overall survival (OS) in patients treated with glasdegib in combination with low-dose cytarabine (LDAC) compared to patients receiving LDAC alone. The present analysis estimated the budget impact of including glasdegib combined with LDAC as first-line treatment for these AML patients from a US health plan perspective. Methods The budget impact was assessed using a decision analytic model that compared the current market environment where glasdegib + LDAC was not included with a new market environment where glasdegib + LDAC was included. The comparators in the model were LDAC alone, azacitidine, decitabine, and venetoclax combined with LDAC, azacitidine or decitabine. The budget impact was calculated based on epidemiology inputs, market share inputs, clinical inputs and all relevant cost inputs (i.e. drug and administration cost, medical resource use cost, adverse event cost). The base case was calculated for a US commercial health plan of 1 million members with a time horizon of 3 years. The main outcomes were total costs of current and new market environments, incremental budget impact, incremental cost per member per month (PMPM) and incremental cost per treated patient per month (PTPPM). Both deterministic sensitivity analyses and scenario analyses were performed to assess the uncertainty of the structure and inputs of the model. Results The analysis estimated an eligible patient population of 19 AML patients per year (per million members) who are not candidates for intensive induction chemotherapy. Of these: 2, 4 and 6 patients were estimated to receive glasdegib + LDAC in years 1, 2 and 3, respectively. In the base case, the incremental budget impact of glasdegib + LDAC was $179,290 in year 1, $262,694 in year 2 and $346,098 in year 3. This translated into an incremental cost PMPM of $0.0149, $0.0219, and $0.0288 in years 1, 2, and 3, respectively. The model results were most sensitive to the mean OS of glasdegib + LDAC. Conclusions The introduction of glasdegib + LDAC as a treatment for newly diagnosed AML patients who are not candidates for intensive induction chemotherapy has a small impact on the budget of US payers, given the small size of the eligible patient population. The model results suggest glasdegib + LDAC provides an alternative treatment option while extending life at minimal incremental cost for health plans. As such, glasdegib + LDAC may provide substantial value for money spent on treatment of these AML patients in the US for which treatment options are few. Disclosures Pham: Pfizer: Consultancy, Other: funding from Pfizer. Milev:Evidera: Consultancy, Other: funding from Pfizer. Li:Evidera: Consultancy, Other: funding from Pfizer. Zou:Evidera: Consultancy, Other: funding from Pfizer. Hu:Ingress-health: Consultancy, Employment, Other: funding from Pfizer. Heeg:Ingress-Health: Employment. Bell:Pfizer Inc.: Employment, Equity Ownership.

Description: Introduction: Gemtuzumab ozogamicin (GO; MylotargTM) was approved by the US Food and Drug Administration in 2017 and the European Medicines Agency in 2018 in combination with standard of care (SOC) chemotherapy (daunorubicin/cytarabine) for the treatment of de novo acute myeloid leukemia (AML). Although initial remission rates for de novo AML are high, overall survival (OS) is low; however, a proportion of patients experience long-term remission (〉5 years) and can be considered cured. Statistically cured populations can be estimated by fitting mixture cure models (MCMs) to survival data, a method that takes into account background survival rates. The objective of this research was to assess and compare the statistical cure rates with GO plus SOC vs SOC alone among adult patients with de novo AML. Methods: MCMs (Weibull, lognormal, and gamma) were fitted to patient-level data from the phase 3 ALFA-0701 trial on event-free survival (EFS) and OS of patients with remission (GO plus SOC: n=100; SOC alone: n=96), and OS of all patients (with remission and refractory; GO plus SOC: n=135; SOC alone: n=136). As refractory patients do not experience remission, this methodology would not provide clinically meaningful results since they are unlikely to experience a cure. Analyses for the subgroup excluding patients with adverse cytogenetics were also explored. For the GO plus SOC arm, P values

Description: Introduction: For transplant-ineligible patients (pts) with newly diagnosed MM, the efficacy of VMP was established in the phase 3 VISTA trial. To reduce toxicity of VMP, twice-weekly bortezomib (V) was limited to the first cycle or completely replaced with once-weekly V in subsequent VMP-based trials (GIMEMA MM-03-05, GEM2005MAS65, and ALCYONE), and recent guidelines have recommended a less-intensive VMP schedule (Moreau P, et al. Ann Oncol 2017. 28[suppl_4]:iv52-iv61). In the absence of clinical trials directly comparing the VISTA VMP dosage regimen with modified VMP regimens, a matching adjusted indirect comparison (MAIC) provides a means to compare absolute treatment effects across diverse populations while minimizing the risk of bias associated with a naive indirect comparison. The objective of the present analysis is to compare the efficacy and safety of a modified dosing schedule of V in VMP-based regimens vs the dosing schedule established in VISTA for transplant-ineligible MM. Methods: Primary analysis was a comparison of the VMP schedule of VISTA vs modified VMP schedules pooled from the ALCYONE (once-weekly V during Cycles 2-9) and GIMEMA MM-03-05 trials; only the once-weekly V schedule (Cycles 1-9) from GIMEMA MM-03-05 (GIMEMA-QW) was included in this analysis. GEM2005MAS65 was excluded from the primary analysis because there was no control arm without maintenance (all patients received V-based maintenance after VMP). The supplemental analysis was a comparison of VISTA vs pooled modified VMP schedules from all 3 trials. Individual pt-level data (IPD) were obtained from the sponsor for the VISTA and ALCYONE trials, and a published validated method was used to reconstruct IPD for both progression-free survival (PFS) and overall survival (OS) of the GIMEMA-QW and GEM2005MAS65 trials (Guyot P, et al. BMC Med Res Methodol 2012.12:9). For each analysis, two comparisons were performed, a naive comparison and MAIC. The naive comparison made no adjustments. MAIC comparison weighted individual pts in the VISTA VMP treatment arm to match the baseline characteristics to those in the pooled VMP-modified treatment arms. Available effect modifiers and prognostic factors included age, gender, International Staging System, β2-microglobulin, albumin, serum creatinine, creatinine clearance, and cytogenetic risk. For each pt in the VISTA VMP arm, a weight was attached based on propensity scores. These weights were then used to calculate weighted outcomes. Results: A total of 344 pts received VMP in the VISTA trial and 356, 191, and 130 pts received modified VMP in the ALCYONE, GIMEMA-QW, and GEM2005MAS65 trials, respectively. Baseline demographics and clinical characteristics are provided in Table 1. The primary analysis of VISTA vs pooled data from GIMEMA-QW and ALCYONE revealed that there were no significant differences in median PFS between VISTA (20.7 months) vs GIMEMA-QW and ALCYONE (19.6 months) in the naive comparison (HR: 0.96; 95% CI, 0.77-1.20; P = 0.74) and 23.1 vs 19.6 months in the MAIC (HR: 0.99; 95% CI, 0.76-1.30; P = 0.96; Figure 1A). Similarly, there were no significant differences between the observed overall response rates for the VISTA schedule and the modified VMP dosing schedule for both the naive (75% vs 76%; P = 0.63) and MAIC (77% vs 76%; P = 1.00) comparisons. For OS, survival data from ALCYONE have not yet matured, thus the median OS values for the pooled GIMEMA-QW and ALCYONE data were not reached. Median OS in VISTA was 56.4 months for the naive comparison and 58.1 months for MAIC (naive HR: 0.92; 95% CI, 0.70-1.21; P = 0.54; MAIC HR: 0.94; 95% CI, 0.68-1.28; P = 0.68; Figure 1B). For safety, incidences of peripheral neuropathy were significantly reduced with the modified VMP dosing schedule compared with the VISTA schedule for both the naive (all-grade: 32% vs 47%; P

Description: Introduction Acute myeloid leukemia (AML) is an orphan disease with one of the lowest five-year survival rates among myeloid malignancies in United States adults. Older AML patients face a much lower 5-year survival rate than their younger counterparts (8% for those aged 60-65 years vs. 38% for those under 45 years). Current therapies are limited and historically include low-dose cytarabine (LDAC), decitabine, azacitidine (AZA) and best supportive care. A phase II randomized study (Cortes et al, 2019) among previously untreated AML patients who are not eligible for intensive chemotherapy demonstrated improved overall survival (OS) in patients treated with glasdegib (GLAS) in combination with low-dose cytarabine (LDAC) compared to patients receiving LDAC alone. There are two trials comparing AZA with conventional care regimens that report data by bone marrow blasts (BMB) count: Fenaux et al. (2010) for patients with 20-30% BMB and Dombret et al (2015) for patients with over 30% BMB. In clinical practice, AZA may be restricted to the 20-30% BMB population, which is important to consider when comparing treatment options. Therefore, as there are currently no head-to-head comparisons for GLAS+LDAC vs AZA, two separate indirect treatment comparisons (ITCs) were performed in different BMB populations (i.e., 20-30% and 〉30% BMB). ITCs is an accepted method to support evidence-based comparative effectiveness decision making and ultimately help to optimize treatment and outcomes of patients with previously untreated AML. Method ITCs were conducted in a classical frequentist statistical framework based on the Bucher method. Patient-level data of the Cortes study (data-cut: January 2017) was divided into two subgroups in terms of BMBs, 20-30% (n=30) and 〉30% (n=80) to match the patient population of Fenaux et al (n=34) and Dombret et al (n=399) accordingly. GLAS+LDAC and AZA were compared in terms of overall survival and results were reported in terms of hazard ratio (HR) with corresponding 95% confidence intervals (95% CI). AZA was chosen as the reference treatment in the ITC. Results In the 20-30% BMB population, the estimated OS HR of GLAS-LDAC in comparison to AZA was 0.46 (95% CI: 0.10-2.14). In the 〉30% BMB population, the estimated OS HR of GLAS-LDAC in comparison to AZA was 0.61 (95% CI: 0.35-1.08). Conclusion These ITCs suggest that GLAS+LDAC is trending towards being a better treatment option for improving OS in patients with AML compared with AZA, irrespective of the level BMB. These results are consistent with previously published ITC results for this treatment comparison. The results of this ITC should, however, be interpreted with caution due to methodological limitations. First, the relatively small number of patients and deaths result in high uncertainty (as exemplified by the 95% CIs) and, second, patient baseline characteristics (including cytogenetic risk, ECOG status and de novo status) between trial arms and over the different trials were either imbalanced or not reported. While more research is needed, current evidence suggests that GLAS+LDAC may be the preferred treatment option for previously untreated AML patients irrespective of BMB levels. Disclosures Van Beekhuizen: Ingress-health: Consultancy, Other: funding from Pfizer. Bell:Pfizer Inc.: Employment, Equity Ownership. Gezin:Ingress-health: Consultancy, Other: funding from Pfizer. Cappelleri:Pfizer: Employment, Equity Ownership. Heeg:Ingress-Health: Employment. Selya-Hammer:Pfizer Inc: Employment, Equity Ownership. Charaan:Pfizer Inc: Employment, Equity Ownership. Chan:Pfizer Inc: Employment, Equity Ownership.

Description: Background: In patients with newly diagnosed multiple myeloma (ndMM) who are ineligible for autologous stem cell transplantation (ASCT), bortezomib, melphalan, and prednisone regimen (VMP) is standard of care as a first-line treatment in most regions of the world. Daratumumab is a new monoclonal antibody aimed to improve outcomes in ndMM. The ongoing ALCYONE study demonstrated significant improvement in progression-free survival (PFS) and overall response rate (ORR) for the combination of daratumumab plus VMP (D-VMP) compared to VMP in transplant-ineligible ndMM patients (Mateos, 2018). While direct head-to-head randomized controlled trials (RCTs) are lacking, it is important to assess how D-VMP compares with other treatment regimens used in clinical practice for ndMM patients who are ineligible for ASCT. Aims: The aim of this study is to investigate the comparative effectiveness (PFS, ORR) of D-VMP with other relevant treatment regimens used in patients with ndMM who are ineligible for ASCT. Methods: We conducted a Bayesian network meta-analysis (NMA) based on RCTs identified through a systematic literature review (SLR). Both fixed effects and random effects models were tested. The results are depicted in a network of evidence, forest plots, ranking histograms and probabilities of D-VMP being better than the comparator treatment regimens. Results: The SLR revealed 25 RCTs conducted in patients with ndMM who are ineligible for ASCT. For PFS, the NMA included 20 RCTs covering 20 treatments and for ORR, the NMA included 20 RCTs covering 21 treatments. Random-effects model is preferred for PFS as well as for ORR as this model showed lower deviance information criterion (DIC), and as the homogeneity assumption was violated for PFS. The results for both PFS and ORR are summarized in Table 1. For PFS and ORR, D-VMP ranked first in the evidence of network. For PFS, D-VMP was statistically significantly more effective compared to 10 out of the 19 treatment regimens. For ORR, D-VMP was significantly more effective as compared to 12 out of the 20 treatment regimens. Conclusion: In the absence of head-to-head RCTs, NMAs allow delineation of the comparative effectiveness of different treatments. This NMA suggests that D-VMP has a higher potential of being effective in improving ORR and PFS in patients with ndMM who are ineligible for transplant compared to other available treatment options. Updated results based on a 1-year update of ALCYONE will be presented at the meeting. References: Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J; ALCYONE Trial Investigators. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2018 Feb 8;378(6):518-528 Disclosures San-Miguel: Amgen: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria; BMS: Honoraria; Roche: Honoraria. Facon:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Dimopoulos:Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria. Mateos:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cavo:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Heeg:Ingress-health Nederland BV: Employment, Equity Ownership, Research Funding. van Beekhuizen:Ingress Health: Consultancy. Pisini:Janssen Research & Development, LLC: Employment. Nair:Janssen Research & Development, LLC: Employment. Lam:Janssen Global Services, LLC: Employment. Slavcev:Janssen Global Services, LLC: Employment.