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Introduction Plaque psoriasis can significantly impact patients’ quality of life. We assessed psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), developed to capture patients’ experiences of signs, symptoms and impacts of psoriasis. Methods Pooled, blinded, 16-week data from 1002 patients in the BE VIVID and BE READY bimekizumab phase 3 trials were analysed. The suitability of the P-SIM missing score rule (weekly scores considered missing if ≥ 4 daily scores were missing) was assessed. Test–retest reliability was evaluated using intraclass correlation coefficients (ICCs). Convergent validity was assessed between P-SIM and relevant patient-reported outcome (PRO) (Dermatology Life Quality Index [DLQI], DLQI item 1 [skin symptoms], Patient Global Assessment of Psoriasis) and clinician-reported outcome (ClinRO) scores (Psoriasis Area and Severity Index [PASI], Investigator’s Global Assessment [IGA]) at baseline and week 16. Known-groups validity was assessed, comparing P-SIM scores between patient subgroups predefined using PASI/IGA scores. Sensitivity to change over 16 weeks was evaluated; responder definition (RD) thresholds were explored. Results The missing score rule used did not impact P-SIM scores. Test–retest reliability analyses demonstrated excellent score reproducibility (ICC 0.91–0.98). Inter-item correlations at baseline and week 16 were strong (> 0.5), apart from “choice of clothing” with “skin pain” and “burning” at baseline (both 0.49). All P-SIM scores were moderately to strongly correlated with other outcomes, demonstrating convergent validity, apart from ClinROs (PASI, IGA) at baseline that had low variability. P-SIM scores discriminated known groups at week 16, confirming known-groups validity. Changes from baseline to week 16 in P-SIM and other clinically relevant outcomes were strongly correlated (> 0.5; weaker with ClinROs), establishing sensitivity to change. Anchor-based RD analyses determined a four-point P-SIM item score decrease as indicative of marked clinically meaningful improvement. Conclusion P-SIM scores demonstrated good reliability, validity and sensitivity to change. A four-point RD threshold could be used to assess 16-week treatment effects. Trial Registration BE VIVID: NCT03370133; BE READY: NCT03410992. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00570-4.

Introduction This analysis assessed the psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), a novel patient-reported outcome (PRO) tool designed to capture patient experiences of the signs, symptoms and impacts of psoriasis. Methods Blinded data from the BE RADIANT phase 3b trial of bimekizumab were analysed. In BE RADIANT, patients were randomised 1:1 to bimekizumab 320 mg every 4 weeks (Q4W) or secukinumab 300 mg (weekly until Week 4, then Q4W). Three items (itching, skin pain and scaling) of the P-SIM were electronically assessed throughout the trial and were scored from 0 to 10 (none to very severe signs/symptoms/impacts). Test–retest reliability was determined using intraclass correlations. Convergent validity was assessed between P-SIM and other relevant PRO and clinician-reported outcome (ClinRO) scores. Known-groups validity was assessed by comparing mean P-SIM item scores between patient subgroups based on the Psoriasis Area and Severity Index (PASI)/Investigator’s Global Assessment (IGA) scores. Responsiveness was assessed via correlations between changes from baseline in P-SIM item scores and other relevant PRO and ClinRO scores. Anchor-based responder analyses and empirical cumulative distribution function (eCDF) curves determined responder thresholds. Results The three P-SIM items yielded high intraclass coefficients (> 0.70). By Week 48, the three P-SIM items had moderate (> 0.30 and ≤ 0.50) to strong (> 0.50) correlations with other PROs and weaker correlations with ClinROs, demonstrating good convergent validity. For almost all known-group comparisons, statistically significant between-subgroup score differences were seen across all three P-SIM items. Changes from baseline in the P-SIM and other relevant outcomes were above the acceptable threshold of ≤ 0.30, demonstrating sensitivity to change. Anchor-based analyses determined a ≥ four-point reduction from baseline to indicate marked clinically meaningful improvement for the P-SIM. Conclusion These results support the validity, reliability and sensitivity to change of the P-SIM in assessing key symptoms (itching, skin pain and scaling) in patients with moderate to severe plaque psoriasis. Trial registration NCT03536884. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01836-1.

Introduction: Patients (pts) with non-transfusion-dependent β-thalassemia (NTDT) suffer from chronic anemia due to ineffective erythropoiesis. Low hemoglobin (Hb) levels in pts with anemia are associated with development of clinical complications and poor quality of life (QoL). There are no approved treatments for NTDT-associated anemia. Luspatercept has been shown to increase Hb levels in pts with NTDT in the BEYOND study (Taher AT, et al. HemaSphere 2021;5[Suppl 2];Abstract S101). This Hb increase was correlated with improvement in the NTDT Patient-Reported Outcomes (NTDT-PRO) Tiredness/Weakness (T/W) domain. Here we report the effect of luspatercept on red blood cell transfusion (RBCT) burden and QoL outcomes in pts with NTDT in the BEYOND study. Methods: Eligible pts with Hb ≤ 10 g/dL were randomized to luspatercept (1.0-1.25 mg/kg) or placebo (PBO) subcutaneously for ≥ 48 weeks (wk). The disease-specific instrument NTDT-PRO, measuring chronic anemia symptoms in pts with NTDT, was administered to pts as a daily diary starting on the 7 days prior to Dose 1, Day 1, until wk 24, and thereafter over the 7 days prior to dosing at every other dosing visit. The 36-item Short Form Health Survey Version 2 (SF-36 v2) and Functional Assessment of Chronic Illness Therapy-Fatigue, Fatigue subscale (FACIT-F FS) were completed by the pts at screening and at every other dosing visit thereafter starting with day 1, dose 1. Mean change from baseline in NTDT-PRO T/W and Shortness of Breath (SoB) domain scores and in FACIT-F FS score over a continuous 12-wk interval during wk 13 to 24 and wk 37 to 48 was assessed using analysis of covariance (ANCOVA) with treatment group and other relevant covariates in the model. The SF-36 v2 physical component summary (PCS) and mental component summary (MCS) mean change from baseline at wk 24 and wk 48 were analyzed using a mixed-effect repeated measures model with intercept and time as the random effect. The model included change from baseline scores up to wk 48 as the outcome, treatment group assignment, time, baseline scores, randomization stratification factor(s), time-by-baseline score, and time-by-treatment group assignment terms. Descriptive statistics were used to ascertain the number of RBC units, RBCT events, reason for RBCT, and time to first RBCT event. Results: Of 145 pts, 96 were randomized to luspatercept and 49 to PBO. NTDT-PRO analyses were conducted in the intention-to-treat population. The QoL-evaluable populations for FACIT-F FS and SF-36 v2 analyses (luspatercept vs PBO) were: 94 vs 47 and 92 vs 46 pts, respectively. Baseline domain scores of the QoL measures were comparable between the 2 treatment arms. Mean change from baseline (least squares mean [LSM]) in NTDT-PRO T/W domain score (wk 13-24) was −0.68 vs −0.20 for luspatercept vs PBO, respectively (LSM difference [LSMD] −0.48; 95% confidence interval [CI] −1.03 to 0.08; P = 0.0924). Improvement was more pronounced in the luspatercept arm during wk 37-48 (Table). Within the NTDT-PRO SoB domain, mean change from baseline (wk 13-24) was −0.46 vs 0.02 for luspatercept vs PBO, respectively (LSMD −0.49; 95% CI −1.02 to 0.04; P = 0.0721) and during wk 37-48 was −0.59 vs 0.47 for luspatercept vs PBO, respectively (LSMD −1.07; 95% CI −1.80 to −0.33; P = 0.0047) (Table). Favorable QoL improvements were also observed in the luspatercept arm vs PBO and increased over time for both FACIT-F FS and SF-36 v2 assessments (Table). During wk 1-48, 79/96 (82.3%) luspatercept vs 22/49 (44.9%) PBO pts were RBCT-free (P < 0.0001); 5/13 (38.5%) and 1/7 (14.3%) pts treated with luspatercept and PBO, respectively, who received RBCTs at baseline, became RBCT-free during wk 1-48. Among all pts who received RBCTs during wk 1-48, pts receiving luspatercept required fewer RBCTs compared with pts receiving PBO (median 1.0 RBCTs [range 1.0-6.0] vs 2.0 [1.0-7.0], respectively), and fewer RBC units (median 2.0 units [range 1.0-8.0] vs 2.5 [1.0-13.0], respectively). Time to first RBCT (median [range] days) was longer for pts receiving luspatercept vs PBO (336 [2.0-336.0] vs 260.0 [9.0-336.0], respectively) and, in both arms, the main reasons for receiving RBCTs were anemia and surgery. Conclusions: In pts with NTDT, luspatercept improved RBCT burden and QoL compared with PBO. The improvement was more pronounced over time and consistent across 3 QoL-measuring instruments. Most pts receiving luspatercept remained RBCT-free during wk 1-48 of treatment. Figure 1 Figure 1. Disclosures Kattamis: Novartis: Consultancy, Honoraria, Research Funding; Chiesi: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Consultancy, Honoraria; VIFOR: Consultancy; IONIS: Consultancy; Agios Pharmaceuticals: Consultancy; Amgen: Consultancy. Viprakasit: Ionis Pharmaceuticals,: Consultancy, Research Funding; Protagonist Therapeutics: Consultancy, Research Funding; La Jolla Pharmaceuticals: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Vifor Pharma: Consultancy, Research Funding. Cappellini: IONIS Pharmaceuticals: Consultancy; Protagonist Therapeutics: Research Funding; La Jolla: Research Funding; Vifor: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CRISPR Therapeutics: Research Funding. Voskaridou: NOVARTIS: Research Funding; IMARA: Research Funding; BMS: Consultancy, Research Funding; GENESIS: Consultancy, Research Funding; PROTAGONIST: Research Funding; ADDMEDICA: Consultancy, Research Funding. Piga: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acceleron: Research Funding. Porter: Celgene (BMS): Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Silence Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vifor: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria; Protagonism: Honoraria; La Jolla Pharmaceuticals: Honoraria. Coates: UpToDate: Patents & Royalties; Sangamo: Consultancy; Forma Pharma: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Apo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chiesi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vifor Pharma: Consultancy. Forni: Bluebirdbio: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Shetty: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Miteva: BMS: Current Employment. Esposito: Bristol Myers Squibb: Current Employment. Kuo: Bristol Myers Squibb: Current Employment. Guo: Gilead: Consultancy; Janssen: Consultancy; UCB: Consultancy; Daiichi Sankyo: Consultancy; EMD Serono: Consultancy; Bristol Myers Squibb: Consultancy; Evidera: Current Employment. Pelligra: Evidera: Current Employment; Bristol Myers Squibb: Research Funding. Lord-Bessen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Yucel: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Taher: Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Vifor Pharma: Consultancy, Research Funding; Agios Pharmaceuticals: Consultancy; Ionis Pharmaceuticals: Consultancy, Research Funding.

The growing number of disease-modifying treatments (DMTs) for patients with multiple sclerosis (MS) and the high acquisition costs of these DMTs are likely to increase the demand for information on their cost effectiveness. To improve the comparability and applicability of the findings from future cost-effectiveness analyses, it would be useful to have a clear understanding of the methodological challenges of modelling the cost effectiveness of DMTs in MS and the different approaches taken by such studies to date. In contrast to previous review studies, this review focuses on long-term time horizon (≥10 years) simulation-based cost-effectiveness analyses with homogeneous contexts of analysis (i.e. those with similar study objectives, comparators, and target populations) published over the past decade. By doing so, it provides a clearer picture of how modelling approaches taken in the existing studies truly differ across studies, and reveals major areas for improvement in conducting future cost-effectiveness analyses of DMTs for patients with MS.

Introduction: Anemia occurs in 80-90% of patients with myelodysplastic syndromes (MDS), nearly half of whom are red blood cell (RBC) transfusion dependent (TD) at diagnosis. The presence of anemia, transfusion dependency, and the resulting complications exacerbate the burden of MDS. Patients with lower-risk MDS have longer overall survival (OS) than patients with higher-risk MDS; however, TD status and higher transfusion load significantly reduce OS. Treatment of lower-risk TD MDS aims to achieve RBC transfusion independence (TI), hematologic improvements and alterations in erythroid response according to IWG 2006 criteria, and improved health-related quality of life (HRQoL). To evaluate these points, we performed a systematic literature review (SLR) to assess the burden experienced by adult patients with RBC TD anemia in lower-risk MDS. Methods: Embase®, MEDLINE®, and the Cochrane Library were systematically searched from inception to March 2019 to identify observational studies reporting on the HRQoL, clinical, and epidemiological burden as well as treatment patterns for adult patients with lower-risk MDS who were RBC TD. Conference proceedings from the last 2 years were searched to identify recent data not yet published as a full text article. Only English language articles and conference abstracts were included. References were screened at the title/abstract and full-text levels by 2 independent reviewers, with methodology following Cochrane guidelines. Results: Database searches yielded 1,175 records. After removing duplicates, 837 abstracts were reviewed, with 152 publications progressing to full-text review. Ten studies met the eligibility criteria. Two additional records were identified from hand searching (Figure). Many studies reported on mixed MDS patient populations, where only a subset were lower-risk and TD, limiting the amount of data available. Nine studies were from the USA or EU5 (France Germany, Italy, Spain, United Kingdom) as well as 1 international study encompassing Europe, the USA, and Australia. The majority of studies defined risk status using the International Prognostic Scoring System (IPSS) risk score, with only 1 study reporting both IPSS and Revised-IPSS (IPSS-R) score. Where reported, patients were mostly older (mean age > 70 years). Burden data were sparse, with few outcomes reported across multiple studies (Table). One study from Italy (mean age 72 years) reporting EuroQoL 5-dimension Visual Analogue Scale data indicated that patients with TD MDS had worse scores (53.0) compared with patients aged 65-74 years in the general Italian population (67.8). Clinical data indicated a variable OS rate across studies conducted in Spain and France, as well as in the 1 international study, with a 2-year OS rate of 73.2% and 4-year OS rates ranging from 27.6% to 73%. The data consistently reported that patients with TD MDS had shorter OS than patients with TI MDS. Differences in timepoints for assessment, types of treatments, and RBC transfusion load increased the variation in OS data. TI was defined as a transfusion-free period of ≥ 56 days, or 8 weeks, in most studies. Median time to reach TI (when reported) ranged from 32-97 weeks, although the prolonged length of time it took to reach TI and the proportion of patients achieving TI indicated an extensive time on treatment. Similar conclusions were drawn in 3 studies that compared OS in patients who became TI with those who remained TD. Epidemiology data were limited to mortality data, and no data were available on morbidity, incidence, or prevalence of disease. Mortality data provided an incomplete picture; deaths were reported as overall mortality or non-leukemic deaths, obscuring mortality rates specifically associated with lower-risk TD MDS. Treatment patterns were reported in 3 studies; erythropoiesis-stimulating agents and hypomethylating agents were the most common treatments reported. Conclusions: Data on the burden of illness in patients with lower-risk MDS with TD anemia were limited and reported inconsistently across studies. Despite this heterogeneity, HRQoL outcomes had a trend toward worse scores in patients with TD MDS than in the general population. OS rate at 2 and 4 years indicated worse prognosis in patients with TD MDS compared with the general population. To better understand the burden of illness, further robust observational studies are needed to close the evidence gaps in this population. Disclosures Deshpande: Evidera: Employment; Celgene Corporation: Consultancy. Turner:Evidera: Employment; Celgene Corporation: Consultancy. Byrnes:Evidera: Employment. Pelligra:Celgene Corporation: Research Funding; Evidera: Employment. Rines-MacEachern:Evidera: Employment. Chitnis:Celgene Corporation: Consultancy; Evidera: Employment. Kulasekararaj:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Achilleon: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Akari Therapeutics: Consultancy. Tang:Celgene Corporation: Employment, Equity Ownership. Morison:Celgene Corporation: Employment. Oliva:Apellis: Consultancy; Celgene Corporation: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

Introduction: Adults with transfusion-dependent (TD) anemia due to β-thalassemia experience significant side effects and increased mortality due to iron overload resulting from repeated red blood cell (RBC) transfusions. To characterize the burden associated with TD anemia in adults with β-thalassemia, a systematic literature review (SLR) was conducted to gather data on the clinical, health-related quality of life (HRQoL), economic, and epidemiological burdens, as well as treatment patterns for patients with TD anemia due to β-thalassemia. Methods: Systematic searches (covering the period from database inception to April 2019) were executed in MEDLINE®, Embase®, and the Cochrane Library for observational studies on the burden of illness in adult patients with TD anemia associated with β-thalassemia. Conference proceedings from the last 2 years were searched to identify recent data not yet published in full text. References were screened at the abstract and full-text levels by 2 independent reviewers, with methodology following Cochrane guidelines. Results: Searches of electronic databases yielded 1,252 citations. After removing duplicates, 874 abstracts were reviewed, with 72 publications progressing to full-text review. Five publications from database searches that met the eligibility criteria were included. An additional 11 references were identified for inclusion from hand searching and conference proceedings, resulting in 16 total references reporting on 13 unique study populations (Table, Figure). Study population sizes ranged from 14 to 1,548 patients, with mean ages varying from 19 to 43 years when reported. Definitions of transfusion dependence were reported in 5 studies; 3 studies defined transfusion dependence as receipt of ≥ 8 RBC transfusions over a 1-year period. Clinical outcomes were rarely reported across studies; 1 study reported survival over time (overall survival [OS] of 96% at 1 year, 86% at 2 years, and 71% at 3 years, with no significant differences by sex). Use of iron chelation therapy (ICT) varied from 63.6% to 100% in 5 studies; 1 study reported that 72% of patients received oral iron chelators, 30% received injectable iron chelators, and 14% received both oral and injectable ICT. Mean total annual cost per person for treating patients with β-thalassemia who received regular RBC transfusions was $128,062, significantly higher than for matched controls ($5,438; P < 0.001). The main cost drivers were ICT (48%) and RBC transfusions (31%). Hospitalizations related to transfusions varied widely within and across studies. Instruments that were used to assess patient HRQoL included the SF-36, BPI Short Form, TranQoL, and FACT-An; results were inconsistent across studies. Most studies indicated that β-thalassemia impacted HRQoL relative to the general population. Relative to normative US data (50), patients with β-thalassemia had lower SF-36 scores in role-physical (47.33), social functioning (46.79), role-emotional (46.78), physical component summary (46.8), and for general health (41.5). Patients were found to experience transfusion-related pain throughout the transfusion cycle, with increased pain associated with higher transfusion frequency. A cross-sectional study found that families of patients with β-thalassemia experienced substantial caregiver burden, including employment and financial problems affecting nearly half of families and a high level of parental anxiety. Epidemiological studies were limited to sparse mortality and comorbidity data and did not present data on the incidence or prevalence of adults with TD anemia in β-thalassemia. Mortality in patients with thalassemia major was 12.8%; primary comorbidities were osteoporosis (16%-100%) followed by cardiac disease (30%), hypogonadism (22%), hypothyroidism (12%) and depression (2%). Conclusions: TD β-thalassemia affects multiple areas of a patient's life and well-being. Although limited data were available for the adult population, studies suggested a significant burden affecting the HRQoL and economic outcomes of patients with TD β-thalassemia in countries around the world. To better understand the burden of illness in TD β-thalassemia, further high-quality observational studies on treatment patterns and epidemiology, as well as those on the clinical, HRQoL, and economic burdens, are needed to close the evidence gaps identified by this SLR. Disclosures Turner: Evidera: Employment; Celgene Corporation: Consultancy. Deshpande:Celgene Corporation: Consultancy; Evidera: Employment. Chitnis:Celgene Corporation: Consultancy; Evidera: Employment. Byrnes:Evidera: Employment. Pelligra:Evidera: Employment; Celgene Corporation: Research Funding. Rines-MacEachern:Evidera: Employment. Morison:Celgene Corporation: Employment. Tang:Celgene Corporation: Employment, Equity Ownership.

Background: Lenalidomide and low-dose dexamethasone (Rd)-based therapies are widely used in the USA, while both Rd and bortezomib, melphalan, and prednisone (VMP) are used in Europe as first-line treatments (Txs) for patients (pts) ineligible to receive ASCT (Moreau P, et al. Ann Oncol. 2017;28:52-61). Of these, only Rd has the advantage of being an oral therapy which stimulates the immune system, is non-stem cell toxic, and has demonstrated both progression-free survival (PFS) and overall survival (OS) advantages compared with melphalan, prednisone and thalidomide (MPT). Rd is generally well tolerated, enabling pts to benefit from continuous therapy in contrast to the fixed duration employed for VMP. Newer regimens, such as the quadruplet daratumumab (Dara) in combination with VMP, have shown improved PFS vs VMP in the ALCYONE study, however, are yet to demonstrate an OS benefit (Mateos MV, et al. N Engl J Med. 2018;378:518-28). No study has compared VMP + Dara with Rd. Although clinical considerations are important in Tx decisions, combination regimens involving newer agents tend to add costs and require demonstration of significant added value to be considered cost-effective, especially given their potential impact on health system budgets. This analysis assessed the cost-effectiveness of Rd vs VMP, and compared these regimens with VMP + Dara, as first-line therapy for NDMM pts ineligible for ASCT from the perspective of the national health services (NHSs) of EU5 countries. Methods: A partitioned survival model was developed to model PFS and OS over a lifetime horizon. PFS and OS parametric functions for Rd were derived using published real-world Kaplan-Meier curves. A network meta-analysis was conducted to derive hazard ratios (HRs) for Rd vs VMP + Dara and vs VMP. In the absence of OS data for VMP + Dara, any advantages in survival are unknown. For the purposes of this analysis, a conservative estimate of OS equivalency compared with Rd was used, yet a range of values are possible. Drug acquisition costs were sourced from national drug price databases. Resource utilization costs were sourced from UK NHS reference costs and converted to EU5 country costs using producer price indices published by OECD; an average of all EU5 country costs was used. EQ-5D utilities for pre- and post-progression disease states were taken from Ramsenthaler C, et al. BMC Cancer. 2016;16:427. Disutilities for regimens requiring subcutaneous injections and intravenous infusions were applied (Stopeck A, et al. J Med Econ. 2012;15:712-23). Results: The base case analysis produced a total number of 3.17, 2.23, and 3.12 quality-adjusted life years (QALYs) for Rd, VMP, and VMP + Dara, respectively. The incremental cost-effectiveness ratio (ICER) for Rd vs VMP was EUR 43,030/QALY, indicating that Rd is cost-effective vs VMP at a willingness-to-pay threshold of EUR 50,000/QALY. Rd dominates VMP + Dara, having a greater gain in QALYs at lower cost. The ICER for VMP + Dara vs VMP was EUR 202,903, well above any acceptable cost-effectiveness threshold in Europe. Discussion: Achieving durable remission while minimizing toxicities in first-line Tx is an important Tx goal, as it has a bearing on the subsequent Tx journey both from an outcome and cost perspective. Individual country pharmacoeconomic assessments have shown Rd is cost-effective vs VMP (SMC No 1096/15, 2015; AWMSG advice 2116, July 2016; Usmani SZ, et al. J Med Econ. 2016;19:243-58), and a recent cost impact analysis suggested substantial cost savings with Rd use relative to VMP + Dara at first-line Tx (Jackson G, et al. HemaSphere 2018;2:PS1429). Limited clinical data and experience with VMP + Dara mean that estimates of long-term clinical outcomes (e.g. OS) associated with this regimen and costs of managing adverse events are not fully known and may not accurately reflect outcomes in clinical practice. In contrast, PFS and OS benefits for Rd vs MPT have been demonstrated (Facon T, et. al Blood. 2018;131:301-10), and an indirect Tx comparison reported statistically significant PFS and OS benefits for Rd vs VMP (Weisel K, et al. Leuk Lymphoma. 2017;58:153-61). As additional regimens are evaluated to assess clinical benefits over current standards of care, cost-effectiveness analyses are warranted to help define their place in the management of NDMM. For example, it may be interesting to compare Rd and Rd-based triplet regimens with VMP + Dara once relevant clinical data become available. Disclosures Ashcroft: Janssen: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria; Amaris Medical: Consultancy, Honoraria. Shephard:Celgene: Consultancy; Amaris Consulting: Employment. Elnoursi:Celgene: Consultancy; Amaris Consulting: Employment. Pelligra:Evidera: Employment. Dhanasiri:Celgene International: Employment, Equity Ownership.

INTRODUCTION: Several new agents and regimens are available for the treatment of relapsed refractory multiple myeloma (RRMM). Comparison of all these is not feasible, yet therapeutic selections need to be made for optimal patient care. Both the MM-002 (Richardson et al., 2014) and MM-003 (San Miguel et al., 2013) trials have demonstrated the clinical benefits of pomalidomide plus low-dose dexamethasone (POM+LoDEX) in improving survival outcomes for patients with RRMM who had received ≥2 prior lines of therapy. Daratumumab (DARA) monotherapy was approved in the US for the treatment of RRMM patients, based on the results of a single-arm trial (SIRIUS) (Lonial et al., 2016). To date, there are no head-to-head studies comparing POM+LoDEX with DARA. We performed an indirect comparison of the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) between POM+LoDEX and DARA in RRMM patients with ≥2 (median of 5) prior lines of therapy. METHODS: Matching-adjusted indirect comparison (MAIC) (Ishak et al., 2015; Signorovitch et al., 2012) is a method used to conduct indirect comparisons between relative efficacies of treatments after adjusting for imbalances across trials where the study populations were roughly similar. To perform a MAIC, it is necessary that the selected studies are compatible. Both MM-002 and SIRIUS were phase II trials and included mainly patients from North America, while other geographic regions were more widely represented in the phase III MM-003 trial. Thus, the MAIC was conducted using individual patient data from the intention-to-treat (ITT) population of POM+LoDEX from MM-002 and published aggregate data on patient characteristics and outcomes for the ITT population of DARA from SIRIUS. A propensity-score logistic regression equation was used to re-weight the POM+LoDEX patients such that their aggregate characteristics matched exactly those in SIRIUS for all prognostic factors (i.e., full set) which were available in both studies. These factors included age, gender, race, disease duration, immunoglobulin heavy chain type, Eastern Cooperative Oncology Group (ECOG) performance status, plasmacytoma, creatinine clearance, number of prior therapy lines, prior stem cell transplantation, and refractoriness to bortezomib, lenalidomide, or both. The relative treatment effects were estimated with a weighted logistic regression model for ORR and weighted Cox regression models for PFS and OS. Sensitivity analyses were also conducted by matching on only important prognostic factors (i.e., reduced set), identified from multivariate regression analyses for each endpoint. RESULTS: MM-002 and SIRIUS were generally similar in design and had sufficient overlap in baseline characteristics to allow adjustment for potential confounding. Most prognostic factors were similar between the two arms. However, patients on POM+LoDEX had worse ECOG status, while more patients on DARA had a plasmacytoma and creatinine clearance CONCLUSIONS: This analysis suggests that POM+LoDEX and DARA have similar clinical benefits with respect to ORR, PFS, and OS in RRMM patients with ≥2 prior lines of therapy. Treatment choice may be made between these two based on factors other than efficacy alone. MAIC analysis may be helpful in therapeutic decisions where direct comparative trials are not available, however as with any non-randomized study potential for residual confounding may still exist. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership, Research Funding. Proskorovsky:Evidera: Employment, Other: As a salaried Evidera employee, I am not allowed to accept any remuneration or honoraria. Evidera received funding from Celgene.. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Krotneva:Evidera: Employment, Other: As a salaried Evidera employee, I am not allowed to accept any remuneration or honoraria. Evidera received funding from Celgene.. Page:Evidera: Other: As a salaried Evidera employee, I am not allowed to accept any remuneration or honoraria. Evidera received funding from Celgene.. Pelligra:Evidera: Employment, Other: As a salaried Evidera employee, I am not allowed to accept any remuneration or honoraria. Evidera received funding from Celgene.. Guo:Celgene: Consultancy. Mouro:Celgene: Employment, Equity Ownership. Ailawadhi:Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy.