No abstract

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.

Background: There are sparse data addressing whether standard risk factors for febrile neutropenia (FN) are relevant in patients receiving myelosuppressive chemotherapy and primary prophylaxis for FN, which would have implications for variables to consider during real-world comparative analyses of FN incidence.Objective: To assess the impact of baseline patient-specific risk factors and regimen risk on the incidence of FN in patients receiving pegfilgrastim primary prophylaxis. Methods:This was a retrospective observational study in patients with breast cancer (BC) who received myelosuppressive chemotherapy and prophylactic pegfilgrastim identified January 1, 2017-May 31, 2018 from MarketScan® research databases. The outcomes were defined as incidence of FN in the first cycle and among all cycles of chemotherapy using three different definitions for FN. Logistic regression and generalized estimating equations models were used to compare outcomes among patients with and without patient-specific risk factors and among those receiving regimens categorized as high-, intermediate-, or other-risk for FN (low-risk or undefinable by clinical practice guidelines).Results: A total of 4460 patients were identified. In the first cycle of therapy, patients receiving intermediate-risk regimens were at up to 2 times higher risk for FN across all definitions than those receiving high-risk regimens (P<0.01). The odds ratio for main FN among patients with ≥4 versus 0 risk factors was 15.8 (95% confidence interval [CI]: 1.5, 169.4; P<0.01). Patients with ≥3 FN risk factors had significantly greater risks for FN across all cycles of treatment than those with no risk factors; this was true for all FN definitions. Discussion:The choice of FN definition significantly changed the impact of risk factors on the FN outcomes in our study, demonstrating the importance of evaluating all proxies for true FN events in a database study. This is particularly important during real-world study planning where potential missteps may lead to bias or confounding effects that render a study meaningless. Conclusions:In patients with BC receiving chemotherapy with pegfilgrastim prophylaxis, patientspecific risk factors and regimen risk levels are determinants of FN risk. In real-world studies evaluating FN incidence, it is imperative to consider and control for these risk factors when conducting comparative analyses. 107Li E, et al. JOURNAL OF HEALTH ECONOMICS AND OUTCOMES RESEARCHdepends on the chemotherapy regimen, dose intensity, and patientspecific risk factors. 5 Clinical practice guidelines published by the National Comprehensive Cancer Network (NCCN) stratify chemotherapy regimens into three FN risk categories as high risk (>20%), intermediate risk (10%-20%), and low risk (<10%) based on the agents, dose, and patient-specific risk factors. Employing these categories, they recommend the use of granulocyte colony-stimulating factors (G-CSFs), including short-acting (eg, filgrastim) and long-acting (eg, pegfilgrastim) formulations, as primary FN proph...

Background Extended first‐line therapy (1LT) has improved clinical outcomes in newly diagnosed multiple myeloma (NDMM). This retrospective study of NDMM patients evaluated the relationship between dose‐attenuation of 1LT and duration of therapy (DOT) and DOT on outcomes. Methods Adults with NDMM not undergoing stem cell transplant (SCT) from January 1, 2012 toMarch 31, 2018 from the Integrated Oncology Network were included; 300 were randomly selected for chart review. 1LT DOT, time to next treatment (TTNT), progression‐free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier analysis. Marginal structural models evaluated relationships between DOT and TTNT, PFS, and OS at 2 years accounting for confounders and survival bias from the time‐dependent nature of DOT. Results Of 300 chart‐reviewed patients, 93 were excluded for incomplete data or meeting exclusion criteria. Among 207 NDMM patients, median age was 74 years; 146 (70.5%) did not receive dose‐attenuation during 1LT. Patients with short DOT were older, frailer, with a higher comorbidity burden, and a significantly lower proportion had an Eastern Cooperative Oncology Group PS = 0. As DOT increased, more patients underwent dose‐attenuation ( p < 0.0001). The median 1LT DOT was 20.9 (95% confidence interval [CI]: 13.9, 26.4) versus 4.2 months (95% CI: 3.2, 4.9) for patients receiving versus not receiving dose‐attenuation, respectively ( p < 0.0001). After accounting for survival bias, confounder‐adjusted TTNT was prolonged with each additional month of 1LT (odds ratio [OR]: 0.76 [95% CI: 0.75, 0.78]); likelihoods of risks of disease progression (OR: 0.87 [95% CI: 0.86, 0.88]) and death at 2 years (OR: 0.72 [95% CI: 0.70, 0.74]) were reduced with each month of 1LT ( p < 0.0001 for all outcomes). Conclusions Dose‐attenuated 1LT was associated with longer DOT among patients with non‐SCT NDMM. Each additional month of 1LT was associated with a reduced adjusted likelihood of disease progression and death at 2 years. Dose‐attenuation of 1LT can extend DOT; longer DOT may improve clinical outcomes.

Background: There are sparse data addressing whether standard risk factors for febrile neutropenia (FN) are relevant in patients receiving myelosuppressive chemotherapy and primary prophylaxis for FN, which would have implications for variables to consider during real-world comparative analyses of FN incidence. Objective: To assess the impact of baseline patient-specific risk factors and regimen risk on the incidence of FN in patients receiving pegfilgrastim primary prophylaxis. Methods: This was a retrospective observational study in patients with breast cancer (BC) who received myelosuppressive chemotherapy and prophylactic pegfilgrastim identified January 1, 2017-May 31, 2018 from MarketScan® research databases. The outcomes were defined as incidence of FN in the first cycle and among all cycles of chemotherapy using three different definitions for FN. Logistic regression and generalized estimating equations models were used to compare outcomes among patients with and without patient-specific risk factors and among those receiving regimens categorized as high-, intermediate-, or other-risk for FN (low-risk or undefinable by clinical practice guidelines). Results: A total of 4460 patients were identified. In the first cycle of therapy, patients receiving intermediate-risk regimens were at up to 2 times higher risk for FN across all definitions than those receiving high-risk regimens (P<0.01). The odds ratio for main FN among patients with ≥4 versus 0 risk factors was 15.8 (95% confidence interval [CI]: 1.5, 169.4; P<0.01). Patients with ≥3 FN risk factors had significantly greater risks for FN across all cycles of treatment than those with no risk factors; this was true for all FN definitions. Discussion: The choice of FN definition significantly changed the impact of risk factors on the FN outcomes in our study, demonstrating the importance of evaluating all proxies for true FN events in a database study. This is particularly important during real-world study planning where potential missteps may lead to bias or confounding effects that render a study meaningless. Conclusions: In patients with BC receiving chemotherapy with pegfilgrastim prophylaxis, patient-specific risk factors and regimen risk levels are determinants of FN risk. In real-world studies evaluating FN incidence, it is imperative to consider and control for these risk factors when conducting comparative analyses.