Parikh, Kejal

Abstract Introduction: There have been substantial advances in treatment options for multiple myeloma (MM) over the past 15 years, yet little real-world evidence is available to describe the recent trends in MM treatment costs and outcomes. This study aimed to examine the trends in novel therapy use, total healthcare costs, and survival outcomes among newly diagnosed MM patients in the US since 2000. Methods: Patients aged ≥18 years who had ≥ 2 medical claims with MM (ICD-9 diagnosis code 203.0x) at least 30 days apart between January 2000 and September 2015 were identified in the Truven Health MarketScan Research Databases. Date of the first medical claim for MM was designated as index date. Patients were required to have 12-month pre-index and 3-month post-index continuous enrollment, and those with claims for MM treatment (including autologous stem-cell transplantation) in the pre-index period were excluded. Controls were selected from a pool of patients without MM and matched 1:1 with MM patients on index year, age, gender and geographic region. Patients whose death event could be obtained from the Social Security Administrations Master Death File were included in the survival outcomes analysis. Total healthcare costs were defined as sum of health-plan and patient paid costs for prescriptions and medical services, including inpatient admissions, emergency room, and physician office visits, and other outpatient services. MM treatment-related drug costs included outpatient pharmacy prescription costs and costs from outpatient services for infused products. Survival time was measured as time from index date to the date of death. Results: 19,417 newly diagnosed MM patients were included (mean± SD age at diagnosis 65.9±12.3 years, 44.9% female), of which 18,260 patients were matched to controls. The percentage of MM patients using novel therapies (pomalidomide, carfilzomib, bortezomib, lenalidomide, or thalidomide) continuously increased from 8.7% in 2000 to 61.3% in 2014. Overall, 28% of MM patients did not receive any treatment within 1-year after diagnosis during the study period. Total per-patient-per-month (PPPM) all-cause healthcare costs increased from $3,263 in 2000 to $14,656 in 2014 among newly diagnosed MM patients, which were primarily driven by costs of outpatient services (Figure 1). Hospitalization costs accounted for 21.5% of total costs in 2000, which increased to 32.7% in 2014. MM treatment-related drug costs accounted for 10.6% of total costs in 2000, 23.6% in 2009, and 28.5% in 2014. Compared with MM patients diagnosed earlier, those diagnosed after 2010 had higher rates of novel therapy use and significantly better survival outcomes (Figure 2); patients diagnosed in 2012 were 1.25 times more likely to survive two years than patients diagnosed in 2006 while two-year survival among controls was fairly stable over the study period (94-97%). MM patients also showed improved survival outcomes over the study period, with the two-year survival gap between MM patients and their matched controls decreasing at a rate of 3% per year. Conclusions: Findings from this study corroborate clinical data suggesting a paradigm shift in MM treatment over the past 15 years that is associated with substantial survival gains. Total healthcare costs among newly diagnosed MM patients have increased steadily since 2000 due to increases in all healthcare cost categories. However, the relative contribution of drug costs has remained fairly stable since 2009 despite new novel therapies coming to market in this time period. Future studies should focus on the impact of specific novel agents on patient survival, the value of clinical benefit engendered, and overall healthcare costs to better inform decision making in this setting. Disclosures Fonseca: Celgene, BMS, Bayer, Novartis, Sanofi, Janssen, Millennium a Takeda Company and AMGEN: Consultancy; Applied Bioscience: Consultancy; FISH: Patents & Royalties: Dr Fonseca has received a patent for the prognostication of MM based on genetic categorization by FISH of the disease. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Bonafede:Truven Health: Other: I am an employee of Truven Health, which received a research contract to conduct this study with Seattle Genetics. . Cai:Truven Health Analytics: Other: I am an employee of Truven Health, which received a research contract to conduct this study with Seattle Genetics. , Research Funding. Parikh:Celgene Corporation: Employment, Equity Ownership, Research Funding. Cosler:Celgene: Consultancy. Richardson:Gentium S.p.A., Jazz Pharmaceuticals: Research Funding; Celgene, Novartis, Millennium Takeda, Gentium S.p.A., Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Abstract The objective of the study was to assess racial disparities in the treatment and outcomes among white, African American, and Hispanic patients with multiple myeloma (MM). Patients with an MM diagnosis from the Surveillance Epidemiology and End Results (SEER)–Medicare (2007-2013) database were included. Continuous Medicare enrollment for 6 months before (baseline) and after MM diagnosis was required unless death occurred. Time from MM diagnosis to novel therapy initiation and autologous stem cell transplant (ASCT), overall survival (OS), and MM-specific survival (MSS) was evaluated. Unadjusted and multivariable regressions compared African Americans and Hispanics vs whites. Trends of novel therapy and ASCT use across MM diagnosis years were assessed using linear regression models. The study included 3504 whites, 858 African Americans, and 468 Hispanics. African Americans and Hispanics had a longer time from MM diagnosis to novel therapy initiation vs whites (median: 5.2 and 4.6 vs 2.7 months, respectively). All cohorts had an increasing trend of novel therapy initiation within 6 months of MM diagnosis, particularly whites (all P < .05). Median MSS was significantly longer for African Americans (5.4 years) than whites (4.5 years; P < .05), and was comparable for Hispanics and whites. Median OS was similar overall (2.6-2.8 years). ASCT rate within 1 year of MM diagnosis rose among whites and African Americans (P < .05), but not Hispanics, who were less likely to receive ASCT vs whites. Significant variations in novel therapy and ASCT use were observed among different racial/ethnic groups with MM. Although OS was similar, both African Americans and Hispanics may not be fully benefitting from the introduction of novel therapies, as they receive them later than whites.

Abstract 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 <60 mL/min and were refractory to lenalidomide, bortezomib, or both. After re-weighting, the aggregate patient characteristics for patients receiving POM+LoDEX matched those reported for DARA. The results from the analyses adjusting for all available characteristics showed no statistically significant differences in ORR, PFS, or OS between the two treatments. Similar findings were obtained by adjusting for important prognostic factors only (Table 1). OS results should be interpreted with caution as subsequent treatments cannot be adjusted for in a MAIC analysis. 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.