Clinical impact of transformation to acute myeloid leukemia in patients with higher-risk myelodysplastic syndromes.

Aim: Forty percent of patients with higher-risk myelodysplastic syndromes (HR-MDS) transform to acute myeloid leukemia (AML). Materials & methods: This retrospective study assessed the impact of HR-MDS transformation to AML on OS in a 6-month landmark analysis and the results were validated using a time-varying analysis. Results: The rate of AML transformation was 26.9% at 1 year. Patients who transformed to AML had a higher risk of death than patients who did not in the 6-month landmark analysis (HR: 1.82; p: 0.0072) and time-varying analysis at 1 year (HR: 2.85; p < 0.0001). Patients treated with azacitidine and decitabine in first-line therapy had similar results. Conclusion: HR-MDS transformation to AML is associated with inferior OS in patients with HR-MDS initiating first-line therapy.

Up to 40% of patients with higher-risk myelodysplastic syndromes (HR-MDS) could experience deterioration or progression to acute myeloid leukemia (AML), a type of blood cancer. We conducted a study to assess whether HR-MDS progression to AML had an unfavorable impact on patient life expectancy after initiating treatment for HR-MDS. Our study concluded that patients who experienced progression to AML had a higher chance of dying immediately after their progression to AML than patients who did not. Patients who received azacitidine and decitabine as their first treatment for HR-MDS had similar results.

Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US.

Multiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum's deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.

Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA.

AIM: To evaluate treatment patterns of diffuse large B-cell lymphoma (DLBCL). PATIENTS & METHODS: First-line and relapsed/refractory treatment patterns and survival outcomes following first-line therapy in adult patients newly diagnosed with DLBCL were evaluated. RESULTS: A total of 1436 DLBCL patients initiated treatment and mainly received a combination regimen versus monotherapy (92.1 vs 7.9%). Patients who received monotherapy were older with more comorbidities and had shorter progression-free survival than patients receiving combination therapy (median: 31.3 vs 55.8 months). In the second-line setting (n = 164), rituximab-based combination regimens were most common; 25% underwent stem cell transplantation, and were younger with fewer comorbidities. CONCLUSION: These results illustrate the need for new treatment options for patients unable to tolerate initial combination therapy and transplant-ineligible patients who require salvage therapy.

Real-World Assessment of Interventional Treatment Timing and Outcomes for Varicose Veins: A Retrospective Claims Analysis.

PURPOSE: To evaluate the impact of delaying interventional treatment on varicose vein disease progression, complications, and health care costs in a real-world setting. MATERIALS AND METHODS: This was a retrospective analysis of adults diagnosed with varicose veins between January 2008 and June 2010. Patients were followed for 2 years after diagnosis and categorized into three cohorts based on the timing of interventional therapy: early (≤ 2 mo), intermediate (> 2 mo but ≤ 6 mo), and late (> 6 mo). Disease progression and all-cause health care costs were evaluated. RESULTS: A total of 44,206 patients were included, with 43% classified as receiving early interventional therapy, 33% as intermediate, and 24% as late. Early interventional treatment was associated with lower disease progression rates (29.2%) compared with intermediate (42.5%; P < .0001) and late treatment (52.2%; P < .0001). Also, early interventional treatment was associated with lower costs ($17,564) than intermediate ($17,923; P > .05) and late treatment ($18,399; P < .05). Each 30-day delay in treatment initiation was associated with a 7% higher risk of disease progression (P < .0001) and a 1% increase in costs (P < .0001). CONCLUSIONS: Findings suggest that early initiation of interventional varicose vein treatment was significantly associated with a decreased risk of disease progression and costs.

Economic Impact of Transformation to Acute Myeloid Leukemia Among Actively Managed Patients with Higher-Risk Myelodysplastic Syndromes in the United States.

INTRODUCTION: Transformation of higher-risk myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) may be associated with increased healthcare resource utilization (HCRU) and costs. To describe this economic impact, HCRU and costs were compared between US patients who experienced transformation to AML and those who did not. METHODS: Using the Optum administrative claims data, this retrospective matched cohort study identified patients (≥ 18 years old) with higher-risk MDS who initiated first-line therapy between January 1, 2008, and June 30, 2019. Patients whose disease transformed to AML were matched 1:1 to patients whose disease did not transform, based on the duration of follow-up. The follow-up period was divided into two periods: pre- (before transformation to AML) and post-AML (after transformation to AML). For patients who did not transform to AML, pre- and post-AML periods were determined using the transformation date of their matched pair. HCRU and total adjusted costs (2019 US dollars, $) were compared between patients who transformed to AML and those who did not. RESULTS: A total of 118 matched patient pairs were included in the study. The hospitalization rate was significantly higher in patients who transformed than in those who did not during the entire follow-up (58.8% vs. 44.1%; P = 0.0295) and post-AML (47.5% vs. 28.0%; P = 0.0028) periods. Across all periods, supportive care use was significantly higher among patients who transformed to AML vs. patients who did not transform. Adjusted mean monthly costs for patients with higher-risk MDS who transformed to AML were higher than those who did not transform ($25,964 vs. $19,150; P < 0.0001). The observed total cost difference was more notable in the post-AML period ($36,424 vs. $14,860; P < 0.0001). CONCLUSIONS: Patients with higher-risk MDS whose disease transformed to AML incurred significantly higher healthcare costs compared to those whose disease did not transform, highlighting the important need for treatments that prevent or delay transformation.

Budget impact of introducing once-every-6-months paliperidone palmitate in US health care plans.

BACKGROUND: In the United States, most patients with schizophrenia have Medicaid coverage. Antipsychotic treatments are the cornerstone of schizophrenia management; most patients are treated with daily oral antipsychotics but struggle with medication adherence. Evidence suggests that medication adherence is inversely correlated with dosing frequency. Once-monthly paliperidone palmitate (PP) has been demonstrated to improve adherence compared with oral antipsychotics; transitioning to once-every-3-months PP (PP3M) further improved adherence. In 2021, once-every-6-months PP (PP6M) was approved by the US Food and Drug Administration to provide even longer between-dose intervals. Public health stakeholders who aim to improve medication adherence are interested in understanding how introducing PP6M to the formulary will impact the budget. OBJECTIVE: To evaluate the budget impact of introducing PP6M to the formulary from the perspectives of a hypothetical US multistate health care payer and state Medicaid programs using California, Georgia, and Ohio as examples. METHODS: The budget impact model was developed from a payer perspective, comparing the reference scenario (without PP6M in the market) with a new scenario (with PP6M). The study population included patients with schizophrenia who were eligible to receive PP6M. Market shares were assigned to the reference and new market scenarios. Efficacy was measured by the relative risk of relapse while receiving treatment. Adherence effects were included in the model and affected costs of treatment and relapse rates. A deterministic 1-way sensitivity analysis was performed. RESULTS: Base-case results for a multistate payer with 1 million members demonstrate that adding PP6M to the market results in total incremental plan-level costs ranging from $7,747 in year 1 to $11,501 in year 5. Increased drug costs were offset by administration and relapse cost savings ($105 and $881 in year 5, respectively). The average incremental cost per treated patient per year was stable at $180.06 for each year, and the incremental cost per member per month stayed below $0.01 for each year. The results of the model from the state-level Medicaid scenarios are broadly similar to those of the multistate base-case perspective. The 1-way sensitivity analysis demonstrated the model is most sensitive to the per-package costs of PP6M and PP3M, along with the proportion of patients fully adherent with PP3M. CONCLUSIONS: The budget impact of introducing PP6M as a treatment option is minimal. With the expected cost offsets from reduced administration and relapse costs due to adherence benefits, these results suggest that PP6M can be a viable treatment option from a clinical and a budgetary perspective. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. The study sponsor provided funds to Xcenda and ApotheCom for medical writing, editorial support, and submission of the manuscript. Hilary Phelps was an employee of Janssen Global Services, LLC, at the time of the development and finalization of the manuscript. Alex Keenan is an employee of Janssen Global Services, LLC, and holds stock in Johnson & Johnson, Inc. Dee Lin and Carmela Benson are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson, Inc. Aditya Raju was an employee of Xcenda at the time of the development and finalization of the manuscript, and Danmeng Huang is an employee of Xcenda, a health care consulting firm that was contracted by Janssen Scientific Affairs, LLC. Chih-Yuan Cheng is an employee of Janssen NV.

Healthcare Costs and Resource Utilization Associated with the Use of Empagliflozin Versus Other Antihyperglycemic Agents Among Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: A Real-World Retrospective Cohort Analysis.

INTRODUCTION: Empagliflozin has demonstrated lower rates of cardiovascular outcomes vs. standard of care among patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). However, the impact of empagliflozin compared to other branded antihyperglycemic agents (AHAs) on total cost of care has yet to be quantified. METHODS AND RESULTS: This retrospective cohort study evaluated the impact of empagliflozin (n = 441) on costs and healthcare resource utilization (HCRU) vs. other branded AHAs (n = 13,122) among patients with T2DM and CVD, using the IQVIA PharMetrics® Plus Claims Database (1 August 2013-31 December 2017). Date of the first prescription (index date) for empagliflozin or other branded AHAs was used to classify patients into study cohorts. All-cause costs and HCRU were computed on a per patient per month (PPPM) basis and compared across study cohorts using outcome-appropriate statistical models. Overall, the empagliflozin cohort was younger and had a lower comorbidity burden. After covariate adjustment, the total all-cause costs (mean difference - $412 PPPM; 95% CI - $593, - $214) were significantly lower for the empagliflozin cohort. These cost differences were mainly driven by lower all-cause medical costs (mean difference - $400 PPPM; 95% CI - $577, - $196). For HCRU, the mean adjusted all-cause visits in the physician office and other outpatient settings were lower with empagliflozin vs. other branded AHAs (p < 0.001). CONCLUSIONS: This study demonstrated that the all-cause healthcare costs and HCRU were significantly lower for patients with T2DM and CVD who initiated empagliflozin vs. other branded AHAs. Along with the positive clinical evidence base of empagliflozin, these results can guide healthcare decision makers during therapy selection.

The effects of oral anticancer parity laws on out-of-pocket spending and adherence among commercially insured patients with chronic myeloid leukemia.

BACKGROUND: Over the past 12 years, 43 states and Washington DC have implemented oral anticancer medication parity laws in response to the burden of pharmacy cost sharing. Parity laws are designed to provide equal coverage and cost sharing between orally and parenterally administered anticancer medications for patients in commercial, fully insured health plans (FIHPs). However, there is considerable state-level variation in the requirements to achieve compliance with parity laws, and the clinical and economic effectiveness of parity is not fully known. OBJECTIVES: To (a) understand the impact of parity laws on out-of-pocket (OOP) spending and adherence to tyrosine kinase inhibitors (TKI) among commercially insured patients with chronic myeloid leukemia (CML) and (b) compare these effects across states with and without per prescription or per 30-day OOP spending limits as part of their parity laws. METHODS: Patients aged 18-64 years with CML, at least 1 pharmacy claim for a TKI, and residence in a state that implemented oral anticancer parity legislation between January 1, 2007, and January 1, 2017, were identified from the IBM MarketScan Commercial Claims and Encounters database. A propensity score-weighted difference-in-difference approach was used to measure the impact of parity on OOP spending and adherence in the 6 months after the first pharmacy claim for a TKI (index date) for patients enrolled in FIHPs (subject to parity) and self-funded health plans (SFHPs; exempt from parity). OOP spending was standardized to a 30-day equivalent amount and adjusted to 2017 US dollars. Adherence was assessed using the proportion of days covered (PDC), and patients were categorized as adherent with PDC ≥ 0.80. RESULTS: Of 1,887 patients initiating a TKI before or after their state's parity law, 678 (35.9%) were enrolled in FIHPs (480 before vs 198 after parity), and 1,209 (64.1%) were enrolled in SFHPs (688 before vs 521 after parity). Implementation of parity laws was not associated with any changes in mean OOP spending; however, it was associated with a reduced likelihood of paying $0 per 30 days across all states (adjusted difference-in-difference [aDD] OR = 0.662; 95% CI = 0.535-0.820) and states without OOP spending limits (aDD OR = 0.654; 95% CI = 0.508-0.848), but not in states with limits. Nonsignificant but directionally opposite changes at each end of the OOP spending distribution were observed for states with and without OOP spending limits, with increased spending observed at the 75th, 90th, and 95th percentiles in states without limits. Mean PDC and adherence showed a nonsignificant increase among FIHP and SFHP patients across all states, states with limits, and states without limits. CONCLUSIONS: Oral anticancer parity laws are not associated with reduced OOP spending or improved adherence in a commercially insured sample of patients with CML. These findings were consistent for states that included OOP spending limits as a component of their parity laws. DISCLOSURES: This study did not receive any external funding. Spargo, Yost, Raju, and Schroader are or were employees of Xcenda, which receives contracts from various industry partners unrelated to this work. There are no other conflicts of interest to disclose.

Impact of changes in reimbursement policies and institutional practice algorithm for utilization of erythropoietic-stimulating agents on treatment patterns and costs in anemic lymphoma patients.

PURPOSE: The objective of this study was to assess the impact of a new evidence-based institutional practice algorithm on the patterns and costs of treatment of chemotherapy-induced anemia (CIA) in lymphoma patients prescribed erythropoietic-stimulating agents (ESAs). METHODS: The study design was retrospective, with a historical control group. Patient demographic data, clinical data (including chemotherapy and hemoglobin values), and cost data were extracted from patient medical charts and institutional databases. Descriptive statistics, t tests, and chi-square analyses were conducted to evaluate the study objectives. RESULTS: The study population consisted of 154 patients, 90 patients in the pre-implementation group and 64 in the post-implementation group. Both groups had similar demographic and baseline clinical characteristics. After implementation, there was a significant decrease in the mean hemoglobin level at the time of subsequent ESA dosing from 9.59 to 8.98 g/dL (P < 0.0001). The proportion of patients who received an ESA at a hemoglobin level >10 g/dL decreased significantly from 66% to 17% (P < 0.0001). There was no significant difference in the mean hemoglobin level at week 4 of ESA therapy, which may indicate that patients were not clinically affected by the change in practice. There were also no significant differences in the number of transfusions administered associated with the treatment of CIA in the study population. CONCLUSIONS: The results of the study show an association between implementation of the new institutional practice algorithm for ESA usage in CIA and a change in ESA utilization patterns.

Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma - Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007-2015.

INTRODUCTION: We characterized real-world treatment patterns in older (65-74 years) and oldest (75-85 years) patients with diffuse large B-cell lymphoma (DLBCL) receiving initial therapy (R-CHOP, non-R-CHOP regimens). Impact of comorbidities on treatment choice, and overall and progression-free survival (OS, PFS) were assessed by age. PATIENTS AND METHODS: Using the Humedica database, we identified 1436 newly diagnosed patients with DLBCL who received frontline therapy from 1/07-9/15. The 885 patients ≥65 years of age were further evaluated for baseline demographics, comorbidities, initial therapy, and PFS/OS. RESULTS: Of 885 patients, 406 (45.9%) were age 65-74, and 479 (54.1%) age 75-85, years. First line therapy was R-CHOP (61.8%) or non-R-CHOP (38.2%). Although Charlson Comorbidity Index (CCI) scores were similar at baseline, congestive heart failure and myocardial infarction were more common in those receiving non-R-CHOP regimens. Survival outcomes were superior for those receiving initial R-CHOP, versus non-R-CHOP, therapy (median PFS 53.9 versus 27.8 months; two-year PFS 71.2% versus 51.6%, p < .0001; median OS not reached versus 45 months; two-year OS 81.3% versus 62.9%, p < .0001, respectively). Only 10.4% (R-CHOP) and 12.1% (non-R-CHOP) of patients received second line therapies. Two-year OS by age (65-74, 75-85 years) was 66.4% and 39.1%, respectively with R-CHOP (p = .0045), and 74.3% and 54.5%, respectively with non-R-CHOP (p = .004), therapy. Age ≥ 75 years and CCI of 2+ were associated with shorter OS and PFS. CONCLUSIONS: This study identified real-world first line treatment patterns for older patients with DLBCL. Our findings support the feasibility of administering standard R-CHOP therapy, even to oldest patients with DLBCL.

Randomized Clinical Trial Representativeness and Outcomes in Real-World Patients: Comparison of 6 Hallmark Randomized Clinical Trials of Relapsed/Refractory Multiple Myeloma.

BACKGROUND: Concern has been increasing in oncology regarding randomized clinical trial (RCT) eligibility limiting the generalizability of the findings to real-world populations. Using a large US electronic health record database, we investigated the real-world generalizability of the findings from recent RCTs for relapsed and/or refractory multiple myeloma (RRMM). PATIENTS AND METHODS: Patients with RRMM initiating second-to fourth-line therapy with the control arm of the following RCTs were retrospectively identified and categorized as "RCT eligible" or "RCT ineligible" according to the eligibility criteria: (1) Rd (lenalidomide, dexamethasone)-ASPIRE, TOURMALINE-MM1, POLLUX, and ELOQUENT-2; and (2) Vd (bortezomib, dexamethasone)-CASTOR and ENDEAVOR. Predictors of RCT ineligibility and overall survival were analyzed using logistic regression and Cox regression analysis. RESULTS: Variations in the individual trial ineligibility rates were noted, with up to 72.3% (range, 47.9%-72.3%) of patients not meeting the eligibility criteria for 1 of the 6 hallmark RCTs (n = 788 for Rd; n = 477 for Vd). Other malignancies, cardiovascular disease, acute infection, and renal dysfunction were the common reasons for ineligibility. Advanced age, Charlson comorbidity score of ≥ 2, later therapy lines (3-4), and refractory status to the previous line were independently predictive of RCT ineligibility. RCT-ineligible versus RCT-eligible patients had a significantly greater mortality risk (hazard ratio, Rd, 1.46; Vd, 1.51). CONCLUSION: Most real-world patients with RRMM were ineligible for the hallmark RCTs. The eligibility rates varied across the RCTs, underlining the flawed nature of cross-study comparisons without RCT validation. Overall survival was significantly affected by the inability to meet the criteria, highlighting the limited generalizability of the RCT results. Greater efforts are required to broaden the eligibility criteria to reflect real-world clinical characteristics and narrow the gap between RCT efficacy and the observed effectiveness in real-world patients with RRMM.

Real-world outcomes and factors impacting treatment choice in relapsed and/or refractory multiple myeloma (RRMM): a comparison of VRd, KRd, and IRd.

Lack of head-to-head trials highlights a need for comparative real-world evidence of proteasome inhibitors plus Rd.Methods: In this retrospective, US population-representative EHR study of RRMM patients initiating IRd, KRd, or VRd in line of therapy (LOT) ≥2 between 1/2014 and 9/30/2018, 664 patients were treated in LOT ≥2 with: IRd, n = 168; KRd, n = 208; VRd, n = 357. Median age was 71/65/71 years; 67%/70%/75% had a frailtymodified score of intermediate/frail; 20%/28%/13% had high cytogenetic risk in I-/K-/V-Rd groups. Risk of PI-triplet discontinuation was lower for I- vs. K-Rd (HR: 0.71) and I- vs. V-Rd (HR: 0.85); unadjusted, median TTNTs (months): 12.7/8.6/14.2 (LOT ≥2) and 16.8/9.5/14.6 (LOT 2-3) (I-/K-/V-Rd). Adjusted TTNT was comparable between I-/K-/V-Rd in LOT ≥2 with a TTNT benefit among intermediate/frail patients for I- (HR: 0.70; P=0.04) and V- (HR: 0.73; P<0.05) vs. K-Rd. I/K/V-Rd triplets were comparable in TTNT overall, but IRd and VRd were associated with longer TTNT in intermediate/frail patients than KRd. The results suggest a trial-efficacy/real-world-effectiveness gap, especially for KRd, underlining the limited generalizability of trial results where >50% of patients are excluded. Individualized treatment based on patient characteristics, such as frailty status, is especially pertinent in an elderly RRMM population.

Adoption of triplet therapy and clinical outcomes in routine practice among newly diagnosed multiple myeloma patients not receiving frontline stem cell transplant in the USA.

BACKGROUND: Immunomodulator (IMID) and proteasome inhibitor (PI) triplet frontline therapy (FT) in newly diagnosed multiple myeloma (NDMM) trials improve overall survival (OS); reported outcomes in routine practice are lacking. Authors compared outcomes in NDMM patients in the USA by use of triplet vs doublet FTs. METHODS: In this retrospective study of NDMM patients without FT transplant between 1/1/2008 and 6/30/2017, FT was categorized as: PI+IMID-triplet (≥ 3 drugs including PI+IMID), non-PI+IMID-triplet (≥ 3 drugs, not PI+IMID), doublet (≤ 2 drugs). Univariate and multivariate analyses identified FT triplet predictors and compared time-to-next-treatment (TTNT)/OS. RESULTS: Among 4,982 NDMM patients, 68% and 32% initiated doublet and triplet FTs (PI+IMID: 36% in 2017). Triplet FT predictors included: age, cytogenetics, ISS stage, certain CRAB symptoms. Median TTNTPI+IMID-triplet = 18.9 months vs 13.7 (non-PI+IMID-triplet) and 16.5 months (doublet) FTs (P< 0.01); adjusted HRPI+IMID-triplet = 0.86; P= 0.009; HRnon-PI+IMID-triplet = 1.10; P = 0.083 vs doublet FT. Median OSPI+IMID-triplet = 58.7 months vs 43.6 (non-PI+IMID-triplet) and 45.7 months (doublet) FTs (P< 0.01); adjusted HRPI+IMID-triplet = 0.83; P= 0.016; HRnon-PI+IMID-triplet = 1.02; P = 0.727 vs doublet FT. CONCLUSION: PI+IMID-triplet FT is not utilized for most non-frontline-transplant NDMM patients in routine care but is associated with prolonged TTNT/OS.

Treatment Patterns and Survival Outcomes in Patients With Follicular Lymphoma: A 2007 to 2015 Humedica Database Study.

BACKGROUND: Few studies have evaluated real-world treatment patterns and survival in follicular lymphoma (FL). This study evaluated these outcomes among newly diagnosed patients with FL in routine clinical care. PATIENTS AND METHODS: A retrospective study was conducted in newly diagnosed patients with FL from Humedica, a large United States electronic medical record database, from January 1, 2008 to July 31, 2015. Patients were followed from treatment initiation until death, loss to follow-up, or end of study (September 30, 2015). Treatment patterns were assessed in the follow-up period. Progression-free survival (PFS) and overall survival (OS) at 2 years were evaluated in the overall population using Kaplan-Meier analyses. OS was also compared between patients with and without evidence of disease progression within 2 years following first-line therapy (ie, early progressors vs. non-early progressors). RESULTS: A total of 1346 patients were included in the study, with most patients receiving rituximab-based regimens. Fewer early progressors received rituximab-based regimens. Across all lines, combination therapies predominated, particularly bendamustine + rituximab. Following first-line therapy, OS was 86.9% at 2 years, and median OS was not reached. Two-year PFS after first-line therapy was 64.6%, and median PFS was 48.1 months (95% confidence interval, 39.4-58.4 months). OS at 2 years was 76.8% among early progressors versus 90.4% among non-early progressors (P < .001); the median OS was not reached in both groups. CONCLUSION: In routine clinical practice, rituximab-based regimens predominated; however, utilization of these regimens differed among early and non-early progressors. The assessment of survival outcomes also highlights the negative impact of early progression on OS in the rituximab-era.

Transfusion-free interval is associated with improved survival in patients with higher-risk myelodysplastic syndromes engaged in routine care.

Most higher-risk myelodysplastic syndrome (HR-MDS) patients will become transfusion-dependent, leading to potential complications, including infections or end-organ dysfunction. Data correlating achievement of transfusion-free intervals (TFIs) during first-line therapy (1LT) with survival are sparse. We evaluated HR-MDS patients receiving 1LT diagnosed from 1/1/2008 to 7/31/2015 and the impact of a TFI (≥60-day interval without transfusions) on progression-free and overall survival (PFS, OS) using Cox proportional-hazard models. Two hundred and twenty-nine HR-MDS patients received 1LT; overall, median PFS/OS were 8.4 months and 14.7 months, respectively. Two-year PFS/OS were 22.3% and 34.6%, respectively. Median PFS/OS were longer for patients with vs. without a TFI (16.9 vs. 6.1 months and 26.1 vs. 11.8 months, respectively; p < .01 [both]). Two-year PFS (43.0% vs. 3.9%; p < .01) and 2-year OS (51.8% vs. 22.5%; p < .01) were also longer in patients with a TFI vs. not. Achievement of a TFI during 1LT appears to positively affect PFS and OS in HR-MDS patients.

Comparison of the Short-Form Survey 12 and the MacNew Heart Disease Health-Related Quality of Life Survey among patients with cardiac disease.

BACKGROUND: Health-related quality of life (HRQL) is an important outcome, especially for chronic diseases with no cure such as cardiovascular diseases. OBJECTIVE: To investigate the comparability of 2 HRQL instruments, the Short Form-12 (SF-12) survey and the MacNew Heart Disease HRQL survey (MacNew) in patients with cardiac diseases. METHODS: A nonexperimental cross-sectional study was conducted in a lipid clinic in the Houston metropolitan area. Patients with a prior cardiac disease were requested to complete the SF-12 and the MacNew scales while waiting to see the physician during their regular clinic visit. Cronbach's alpha values were estimated to evaluate internal consistency. Spearman's correlation was performed to examine the correlation between the SF-12 and the MacNew scale domains. RESULTS: A total of 118 patients were enrolled in this study. High Cronbach's alpha (from 0.89 to 0.94) were observed from all component scores in the MacNew scales. Physical component scores from the SF-12 and from the MacNew were highly correlated (r = 0.74; p < 0.001), as were the mental component score from the SF-12 and the emotional component score from the MacNew (r = 0.68; p < 0.001). CONCLUSIONS: The SF-12 and the MacNew appeared to be strongly correlated to each other for predicting a patient's HRQL in patients with a cardiac disease.

Incremental burden of type 2 diabetes in patients experiencing cardiovascular hospitalizations.

OBJECTIVE: To evaluate the incremental economic burden of type 2 diabetes in patients experiencing cardiovascular (CV) hospitalizations. RESEARCH DESIGN AND METHODS: Adults with ≥1 CV hospitalization were identified using a US-based healthcare claims database from 1 July 2011 to 30 June 2014. Outcomes for patients surviving the index hospitalization were compared between patients with vs. without type 2 diabetes (cohorts were identified in the pre-index period). Subsequent CV hospitalizations were evaluated using Cox proportional hazards models. All-cause and CV-related healthcare resource utilization (HCRU) and costs captured on a per-patient per-month (PPPM) basis during a variable follow-up period were evaluated using appropriate multivariable regression models. RESULTS: Of 316,207 patients with ≥1 CV hospitalization, 23% had comorbid type 2 diabetes. The mean age ± SD was 62.6 ± 12.3 years and 64.4% were male. During follow-up, the type 2 diabetes cohort had a 19% higher risk of subsequent CV hospitalizations compared to the non-type-2-diabetes cohort (p < .001). This difference in risk was highest in patients aged 35-44 years. Subsequent all-cause hospitalizations for the type 2 diabetes cohort were longer (mean length of stay, 6.7 vs. 6.3 days; p < .001), with higher total bed-days PPPM (mean, 0.52 vs. 0.43; p < .001), compared to the non-type-2-diabetes cohort. The type 2 diabetes cohort had a significantly higher incremental cost for both the index CV hospitalization (mean cost difference, $1046; p < .001) and all-cause costs PPPM following discharge (mean cost difference, $749; p < .001). CONCLUSIONS: Comorbid type 2 diabetes was associated with an increased risk of subsequent CV hospitalizations and higher costs and HCRU during the follow-up period.

The impact of age and comorbidities on practice patterns and outcomes in patients with relapsed/refractory multiple myeloma in the era of novel therapies.

OBJECTIVES: One-third of patients with multiple myeloma (MM) are diagnosed at age≥75years. Older patients have increased incidence of cardiovascular disease (CVD) and renal insufficiency (RI), hallmark complications of MM. We examined cumulative incidence of CVD and RI in relapsed/refractory MM (RRMM) and outcomes by age and RI/CVD. MATERIALS AND METHODS: Retrospective cohort study using a large US electronic medical records database of adult patients with RRMM initiating first- and second-line therapy (2LT) between 1/2008-06/2015. RI and CVD comorbidities were based on diagnosis codes and/or lab values. RESULTS: Among 628 patients, 37.1% were ≥75years. Cumulative incidence of CVD and/or RI increased from 47.7% at MM diagnosis to 67.8% at first relapse. Age≥75years had a trend toward higher risk of relapse post 2LT, proxied by time to next treatment (TTNT), (adjusted HR: 1.28; 95% CI: 1.00, 1.65; P=0.05). TTNT was significantly higher with comorbid CVD+RI (adjusted HR: 1.50; 95% CI: 1.11, 2.02; P<0.01). Age≥75years, RI, CVD, and CVD+RI were associated with increased mortality risk from 2LT initiation; adjusted HR: 1.66 (95% CI: 1.19, 2.33; P<0.01), 1.51 (95% CI: 1.01, 2.26; P=0.04), 1.75 (95% CI: 1.03, 2.96; P=0.04), and 1.95 (95% CI: 1.29, 2.93; P<0.01), respectively. CONCLUSION: Despite treatment with novel agents for RRMM in 86% of patients, an outcome gap persists for older patients and those with RI and/or CVD. Personalized treatment approaches that account for age and comorbidities, and further evaluation of innovative regimens and dosing schedules, are needed to improve outcomes for these patients.

Prolonged Duration of Therapy Is Associated With Improved Survival in Patients Treated for Relapsed/Refractory Multiple Myeloma in Routine Clinical Care in the United States.

BACKGROUND: In clinical trials, an extended therapy duration has been associated with better outcomes in patients with newly diagnosed multiple myeloma (NDMM). However, data on how the therapy duration affects the outcomes for patients with relapsed/refractory multiple myeloma (RRMM) are limited. We conducted a large, retrospective study in the United States to evaluate the effect of the duration of second-line therapy on overall survival. PATIENTS AND METHODS: Adults with NDMM from January 2008 to June 2015 were followed up to identify their second-line therapy. The duration of therapy (DOT) and time to next therapy (TTNT), as a proxy for progression-free survival, were estimated using the Kaplan-Meier method. The relationship between the duration of second-line therapy and overall survival was evaluated with a logistic marginal structural model to mitigate the risk of treatment selection and survival bias. RESULTS: A total of 628 NDMM patients developed a relapse after initial therapy. The median DOT for second-line therapy was 6.9 months (95% confidence interval [CI], 5.9-7.7 months), which was shorter than the corresponding TTNT (median, 15.1 months; 95% CI, 13.4-17.3 months). Each additional month of second-line therapy was associated with a reduced adjusted risk of death at 1 year (odds ratio, 0.78; 95% CI, 0.77-0.83; P < .001). CONCLUSION: In a large database capturing a heterogeneous patient population and varied treatment patterns reflecting routine clinical care, we found a clinical benefit for continued longer DOT at first relapse. Despite the emerging paradigm favoring continuous therapy, second-line progression-free survival (utilizing TTNT as the proxy) was more than twofold longer than the DOT. Understanding the barriers to extended DOT could help to improve the outcomes for RRMM patients.

Hypoglycemia Incidence Rates and Associated Health Care Costs in Patients with Type 2 Diabetes Mellitus Treated with Second-Line Linagliptin or Sulfonylurea After Metformin Monotherapy.

BACKGROUND: Hypoglycemia poses a significant clinical and economic burden to patients with type 2 diabetes mellitus (T2DM). Minimizing the risk of hypoglycemia is an important component when managing patients with T2DM. Understanding hypoglycemia rates and the associated economic consequences can help to inform health care decision makers. OBJECTIVE: To assess hypoglycemia incidence rates and associated costs in patients who initiated second-line treatment with the antidiabetic agents linagliptin or a sulfonylurea (SU) after metformin. METHODS: A large U.S. administrative claims database was used to identify patients with T2DM (during the identification period July 2011-October 2013) who initiated linagliptin or a SU after metformin use. The date of the first prescription for linagliptin or a SU during the identification period was designated as the index date. Linagliptin users were matched to SU users based on demographic and clinical characteristics identified within a 12-month period before the index date using propensity scores (1:3 ratio, caliper: ±0.001). Rates and costs (2013 U.S. dollars) of hypoglycemia resulting in any health care resource use were quantified during a variable follow-up period (i.e., end of the study, end of the 12-month follow-up, treatment regimen change, or disenrollment, whichever came first). Hypoglycemia rates per 100 person-years were compared using univariate Poisson regression, and hazard of hypoglycemia was obtained from multivariate Cox proportional hazards regression. Mean monthly hypoglycemia-related costs, all-cause costs, and T2DM-related costs were computed for patients with hypoglycemia and compared using t-tests. RESULTS: Propensity-score matching resulted in a sample of 11,536 patients (linagliptin = 2,884; SU = 8,652) with a mean age of 56 years and 59% male. The rate of hypoglycemia (per 100 person-years) was lower in the linagliptin than the SU user groups (2.51 vs. 3.63; P= 0.049). Linagliptin users had a 33% lower risk of hypoglycemia compared with SU users (HR = 0.67; 95% CI = 0.47-0.97; P= 0.031). Among patients who had hypoglycemia, linagliptin users showed numerically lower mean monthly hypoglycemia-related costs compared with SU users ($300 vs. $890; P= 0.092), which was primarily driven by differences in hypoglycemia-related costs in the hospital setting. A similar theme was observed with monthly all-cause costs (linagliptin users, $1,971 vs. SU users, $3,758; P= 0.092). CONCLUSIONS: Linagliptin use was associated with a lower incidence rate of hypoglycemia compared with SU use in patients initiating second-line therapy after metformin monotherapy. Among patients who experienced hypoglycemia, linagliptin users appeared to have lower monthly hypoglycemia-related and all-cause costs than SU users. Careful consideration of newer treatment alternatives may be prudent for optimal T2DM management, especially with regard to hypoglycemia. DISCLOSURES: Funding for the research study and resultant publication was provided by Boehringer Ingelheim. Shetty is an employee of Boehringer Ingelheim. Cai was an employee of Boehringer Ingelheim at the time of the study. Raju and D'Souza are employees of Xcenda, which received research funding from Boehringer Ingelheim for the conduct of this study and for the preparation of this manuscript. All authors contributed to concept and study design. Raju took the lead in data analysis, along with D'Souza, and all authors contributed equally to data interpretation. The manuscript was written by Raju, D'Souza, Cai, and Shetty and revised primarily by Raju, along with Shetty and D'Souza.