Trends in overall mortality among US veterans with primary myelofibrosis

Abstract

Background Primary myelofibrosis [PMF] is a myeloproliferative neoplasm associated with reduced overall survival (OS). Management strategies for PMF have evolved over the last two decades, including approval of ruxolitinib as the first Janus kinase 1 (JAK1)/JAK2 inhibitor for patients with intermediate or high-risk myelofibrosis. This study assessed changes in mortality before and after ruxolitinib approval, independent of ruxolitinib treatment. Methods This retrospective study investigated mortality trends among US veterans with PMF in 2 time periods, pre-ruxolitinib approval (01/01/2007–12/31/2010) and post-ruxolitinib approval (01/01/2015–09/30/2018). Deidentified patient-level data were extracted from US Veterans Health Administration (VHA) databases using PMF diagnosis codes; index was the first PMF diagnosis date. The analysis included adults with ≥2 PMF claims during the analysis periods who were continuously enrolled in the VHA plan 1 calendar year prior to and 6 months post-index and had ≥1 available International Prognostic Scoring System (IPSS) risk factor (available factors were age > 65, hemoglobin < 10 g/dL, and white blood cell count > 25 × 109/L; each counted as one point). Patients with ≥1 MF diagnosis for 12 months before the index period were excluded. Ruxolitinib treatment was not a requirement to be included in the post-ruxolitinib approval cohort. Mortality rates and OS were estimated using the Kaplan-Meier approach; all-cause mortality hazard ratio was estimated using univariate Cox regression. Results The pre- and post-ruxolitinib approval cohorts included 193 and 974 patients, respectively, of which 80 and 197 had ≥2 IPSS risk factors. Ruxolitinib use in the post-ruxolitinib cohort was 8.5% (83/974). At end of follow-up, median (95% CI) OS was significantly shorter in the pre-ruxolitinib cohort (1.7 [1.2–2.6] years vs not reached [3.4–not reached]; P < 0.001). Overall mortality rates for the pre- versus post-ruxolitinib approval cohorts were 79.8% versus 47.3%, respectively, and overall risk of death was 53% lower in the post-ruxolitinib period (hazard ratio, 0.47; 95% CI, 0.37–0.58; P < 0.001). Mortality rates were lower among patients with < 2 vs ≥2 IPSS risk factors. Conclusions Although veterans with PMF have high overall mortality rates, and results in this population might not be generalizable to the overall population, there was a significant lowering of mortality rate in the post-ruxolitinib period.

Incidence of blast phase in myelofibrosis patients according to anemia severity at ruxolitinib start and during therapy

“…[25][26][27] Despite significant improvements in the survival expectancy of MF patients over the last decades, the incidence of BP has remained unchanged, with no significant impact of RUX monotherapy. [28][29][30][31] This finding was very recently confirmed by an international retrospective data collection where the incidence rate of BP was found to be comparable in a large cohort (n = 1752) of RUX-untreated patients (2.50 %p-y) and in a smaller cohort (n = 273) of RUX-treated patients (2.89 %p-y). 12 In the same study, anemia severity correlated with the incidence of BP, particularly in RUX-unexposed patients, in whom the IRR of BP increased from 1.8 %p-y (anemia grade 0-1) to 4.3 %p-y (anemia grade 3-4).…”

“…Despite significant improvements in the survival expectancy of MF patients over the last decades, the incidence of BP has remained unchanged, with no significant impact of RUX monotherapy 28–31 . This finding was very recently confirmed by an international retrospective data collection where the incidence rate of BP was found to be comparable in a large cohort ( n = 1752) of RUX‐untreated patients (2.50 %p‐y) and in a smaller cohort ( n = 273) of RUX‐treated patients (2.89 %p‐y) 12 .…”

Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT‐I and COMFORT‐II studies

“…Despite this, real‐world treatment patterns indicate that many physicians delay or avoid ruxolitinib treatment, often in favor of hydroxyurea or watchful waiting. In a retrospective study of US veterans with MF in the post–ruxolitinib approval era, only 22.3% of patients with intermediate‐ or high‐risk MF received ruxolitinib 24 . Two other retrospective studies that focused on post–ruxolitinib approval time frames found that hydroxyurea or interferon was used at a similar frequency as ruxolitinib to treat MF, including as a first‐line agent and in patients with intermediate‐2 disease 25,26 .…”

Simultaneous blastic plasmacytoid dendritic cell neoplasm and myelofibrosis: A case report

“…were 79.8 and 47.3%, respectively, and the overall risk of death was reduced by 53% with ruxolitinib approval (16). MF can be secondary to several hematological malignancies, including chronic myeloid leukemia, myelodysplastic syndrome and hairy cell leukemia (17)(18)(19).…”