Patients receiving nilotinib had significantly higher rates of incident T2DM or HLD than patients on dasatinib.

Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox‐Maze IV procedure (CMP‐IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow‐up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat. Methods and Results Between May 2003 and March 2020, 174 consecutive patients underwent a stand‐alone CMP‐IV for longstanding persistent AF. Rhythm outcome was assessed postoperatively for up to 10 years, primarily via prolonged monitoring (Holter monitor, pacemaker interrogation, or implantable loop recorder). Fine‐Gray regression was used to investigate factors associated with atrial tachyarrhythmia (ATA) recurrence, with death as a competing risk. Median duration of preoperative AF was 7.8 years (interquartile range: 4.0–12.0 years), with 71% (124/174) having failed at least one prior catheter‐based ablation. There were no 30‐day mortalities. Freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively. On regression analysis, preoperative AF duration and early postoperative ATAs were associated with late ATAs recurrence. Conclusion Despite the majority of patients having a long‐duration of preoperative AF and having failed at least one catheter‐based ablation, the stand‐alone CMP‐IV had excellent late efficacy in patients with longstanding persistent AF, with low morbidity and no mortality. We recommend consideration of stand‐alone CMP‐IV for patients with longstanding persistent AF who have failed or are poor candidates for catheter ablation.

Background: Metabolic changes such as Type II Diabetes Mellitus (T2DM) and hyperlipidemia (HLD) have been reported in patients receiving BCR-ABL tyrosine kinase inhibitor (TKI) therapy. Incidence of metabolic outcomes in this population has not been evaluated in large, real-world studies. The purpose of this study was to determine incidence and risk for T2DM and HLD in commercially and Medicare insured US patients prescribed dasatinib or nilotinib as first or second line therapy for CML. Methods: A retrospective cohort study using the MarketScan healthcare claims was conducted. Patients ≥18 years with ≥2 inpatient or outpatient claims for CML (ICD-9 205.10-205.12) separated by at least 30 days and ≥1 prescription for dasatinib or nilotinib from July 2006- December 2014 were eligible. Patients were required to have continuous enrollment for ≥6 months prior to the first TKI prescription (index date) and no exposure to a TKI other than imatinib during the pre-index period. No minimum follow-up time was required. First line TKI users were defined as those patients with no imatinib prescription during the pre-index period. Patients with a prescription for imatinib during the pre-index period were considered second line. Two cohorts of patients were studied. Cohort 1 was evaluated for the occurrence of T2DM, defined as ≥2 claims with an ICD-9 code for T2DM or 1 diagnosis claim and an anti-diabetic medication claim. Patients who had a diagnosis of T2DM or received medications for T2DM prior to the index date were excluded from cohort 1. Cohort 2 was evaluated for the occurrence of HLD, defined as ≥2 claims with an ICD-9 code for HLD, or 1 diagnosis claim and an anti-HLD medication claim. Patients with a diagnosis of HLD or medications for HLD prior to the index date were excluded from cohort 2. Patients were evaluated for the outcome of interest (T2DM or HLD) from index date until the outcome of interest occurred, discontinuation of therapy, switch in therapy, end of study (12/31/2014), or end of enrollment, whichever occurred first. To estimate the incidence rates of both outcomes of interest, person years were enumerated from index date until the end of follow up. Incidence rates were computed as the number of events divided by the sum of the person years (PY) at risk for all subjects in the cohort and were reported with associated 95% confidence interval (CI) assuming a Poisson distribution. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) for outcomes while adjusting for age, gender, region, insurance type, index year, Charlson Comorbidity Index (CCI), comorbidities, concomitant medications, and line of therapy. Results: 2,004 patients met inclusion criteria for cohort 1 (n=1,272 dasatinib, n=732 nilotinib), while 1,280 patients met cohort 2 inclusion criteria (n=845 dasatinib, n=435 nilotinib). Baseline characteristics were largely similar between dasatinib and nilotinib patients in each cohort. Significant differences existed in index year, proportion of patients with certain comorbidities and baseline concomitant medications, and percentage of patients receiving the TKI for first line vs second line therapy. Among cohort 1, mean age was 53.4 years and 54.1% were male; median follow-up time was 216 days for dasatinib and 245 days for nilotinib. Incidence rate of T2DM was 17.58 per 1,000 PY (95% CI: 11.14, 26.38) for dasatinib, and 40.36 per 1,000 PY for nilotinib (95% CI: 27.60, 56.98). The HR for occurrence of T2DM (dasatinib as reference) was 2.77 (95% CI: 1.58, 4.86, P=0.0004), indicating patients on nilotinib had a 2.77 times greater risk of developing T2DM while adjusting for baseline characteristics. The mean age of cohort 2 was 48.6 years and 50.3% were male; median follow-up time was 213 days for dasatinib and 206 days for nilotinib. Incidence rate of HLD was 46.41 per 1,000 PY (95% CI: 33.00, 63.45) for dasatinib, and 74.63 per 1,000 PY for nilotinib (95% CI: 50.70, 105.94). The HR for occurrence of HLD (dasatinib as reference) was 1.75 (95% CI: 1.07, 2.87, P=0.025), indicating patients treated with nilotinib had a 1.75 times greater risk of developing HLD after adjusting for baseline characteristics. Conclusions: Patients receiving nilotinib for CML had a higher incidence rate and significantly greater adjusted risk for developing T2DM or HLD than patients receiving dasatinib. Disclosures Franklin: Bristol-Myers Squibb: Consultancy. Burns:Bristol-Myers Squibb: Employment, Equity Ownership. Perez:Bristol-Myers Squibb: Consultancy. Yerragolam:Bristol-Myers Squibb: Consultancy. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership.

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Introduction: PREAMBLE (Prospective REsearch Assessment in multiple Myeloma: an oBservationaL Evaluation) is an ongoing, prospective, multinational, non-interventional observational study to collect information from medical records regarding treatment and diagnostic procedures. By analyzing these data, a better understanding can be gained of the real-world effectiveness of novel agents used in treating relapsed/refractory multiple myeloma (RRMM) and their impact on patient-reported outcomes. This analysis was performed to evaluate comorbidities, treatment patterns, and survival in a PREAMBLE subpopulation that included US patients with MM. Methods: US patients aged ≥18 years with RRMM, ≥1 prior therapy, and initiating treatment with an immunomodulatory drug (IMiD), proteasome inhibitor (PI), or IMiD+PI within 90 days before or 30 days after study enrollment (index therapy) were identified from PREAMBLE. Data were collected at the index healthcare provider visit and every 3 (Year 1) and 6 (Years 2-3) months (mo) over 3 years or until the end of patient follow-up. Data were summarized using descriptive statistics and included age, sex, International Staging System (ISS) stage, type of visits and hospitalizations, disease status, line of therapy, and concomitant disorders. Overall survival (OS) and progression-free survival (PFS) were analyzed using Cox regression and Kaplan-Meier techniques. MM-specific survival was calculated using Cumulative Incidence Function. Results: 239 patients (median age 66 years; 56% male) were enrolled. At the time of data cut-off (7 December 2015), 124 (52%) were still in the study and 115 (48%) had disenrolled, including 71 (62%) who had disenrolled due to death. Median follow-up was 12.0 mo (range, 0.5-37.7). At study entry, 178 (74%) patients had relapsed MM; 140 had ISS stage assigned, with 28% (n=39), 26% (n=36), and 46% (n=65) for Stage I, II, and III disease, respectively. Median time to index therapy since initial diagnosis was 39.6 mo (range, 4.8-174.2). Cardiovascular disease (CVD) was the most common comorbidity (62%) and other comorbidities were highly prevalent as well (Table). At enrollment, most patients were receiving a PI (n=136, 57%; carfilzomib n=68/136, 50%) or an IMiD (n=63, 26%; pomalidomide n=29/63, 46%); 40 patients (17%) were receiving an IMiD+PI (carfilzomib and/or pomalidomide n=11/40, 28%). Median number of prior therapies was 2 (range, 1-10). The overall median PFS was 7.9 mo, with a median PFS for second-line, third-line, and fourth- or greater line of 15.4, 9.0, and 6.9 mo, respectively. Median OS has not yet been reached. 18-mo all-cause mortality was 31.1% (95% CI 24.9-38.5), while 18-mo MM-related mortality was 22.3% (95% CI 16.2-28.4), meaning that at 18 mo, approximately 8.8% of patients died due to non-MM-associated causes (Figure). Death rates were independent of comorbidities and number of lines of prior therapy. A strong association was found between disease status and rate of death: refractory disease was associated with higher death rates (hazard ratio 1.92; 95% CI 1.16-3.16), while sex and ISS stage showed weak association with death rates. Conclusions: The progressively shorter PFS with each successive treatment regimen reflects ongoing development of drug resistance. In this preliminary survival analysis of US patients, the majority of deaths resulted from MM. This finding demonstrates the need for additional treatment options for treating RRMM. CVD was highly prevalent as a comorbidity across all lines of treatment. Figure Figure. Disclosures Vij: Jazz: Consultancy; Karyopharma: Consultancy; Shire: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Novartis: Consultancy. Popov:PAREXEL: Employment. Chen:Bristol-Myers Squibb: Employment.

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