Pf327 Recombinant Factor Viii Fc Fusion Protein in Surgeries in Hemophilia A

Abstract

Background: Vitamin D deficiency has been recently associated, as an independent risk factor, with lower rates of progression-free survival (PFS) and overall survival (OS) in patients with Hodgkin (HL) and non-Hodgkin's lymphoma (NHL). Aims: To investigated the impact of vitamin D status on the outcome of lymphoma patients in two Institutions. Methods: From 2015 to 2018, we tested circulating 25-hydroxyvitamin D3 (25[OH]D3) levels in a prospective cohort of 135 newly diagnosed patients with NHL and HL in two Institutions in Spain. 25[OH]D3 levels were measured by chemoluminescent immunoassay. Determinations were based on guidelines from the Food and Nutrition Board of the Institute of Medicine. According to current guidelines, we considered the following thresholds: vitamin D deficient (<10 ng/ml), vitamin D insufficiency (10 to 30 ng/ml) and normal vitamin D level (>30 ng/ ml). Patients with <20 ng/ml from one Institution had vitamin D substitution. OS and PFS were calculated using Kaplan-Meier estimators, comparison between categories performed by log-rank test and Cox PH regression, and the effect of covariates reported with 95% confidence interval (95 CI). Results: 135 newly diagnosed patients with NHL and HL were included. Median age at diagnosis was 67 years (range, 20 to 91 years). NHL subtypes: 47% diffuse large b cell lymphoma (DBCL), 30% Indolent lymphoma, 5% mantle cell lymphoma, 6% Tcell lymphoma, 10% Hodgkin lymphoma and 3% others NHL 34% had advanced stage and and 39% of NHL patient had ≥ 3score of International Pronostic Index (IPI).55% of the patients were diagnosed in spring or summer. Median 25(OH)D levels at diagnosis were 18 ng/ml. 11% of patients had normal 25(OH)D levels, 77% had insufficient 25(OH)D levels and 12% were deficient at lymphoma diagnosis. Median follow-up was 12 months and 22 deaths were observed. The three groups of vitamin D levels were associated with OS, but this difference was not statistically significant (Figure 1). In the DLBCL subset, we inspected in a Cox Model the effect of Vitamin D levels for OS/PFS, adjusting for IPI Score and vitamin D substitution. Vitamin D levels did not achieve statistical significance for PFS (hazard ratio [HR], 1.02; 95% CI, 0.99 to 1.04) and OS (HR: 0.99; 95% CI, 0.94 to 1.06). Remarkably, there was a tendency towards a better statistically significant outcome in patients supplemented (HR for PFS: 0.36; 95% CI, 0.10 to 1.29; p = 0.10). Summary/Conclusion: Most of our patients present with low levels of vitamin D[JPD1] . In our limited series, with the current follow-up time, baseline vitamin D values did not significantly impact PFS and OS. Further studies are needed to confirm our data.

Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc: Data on safety and effectiveness from phase 3 pivotal studies

“…Real‐world surveillance data from more than 7 years post‐marketing experience 10,11 confirms the risk–benefit profile of rFVIIIFc and rFIXFc established during clinical studies and further underlines the potential for their perioperative use 7,58–64 . An intraindividual comparison of FIX products for orthopedic surgery showed a reduction in number of injections and total factor consumption with rFIXFc versus plasma‐derived FIX 7 .…”

“…[35][36][37][38][39][40] Real-world surveillance data from more than 7 years postmarketing experience 10,11 confirms the risk-benefit profile of rFVIIIFc and rFIXFc established during clinical studies and further underlines the potential for their perioperative use. 7,[58][59][60][61][62][63][64] An intraindividual comparison of FIX products for orthopedic surgery showed a reduction in number of injections and total factor consumption with rFIXFc versus plasma-derived FIX. 7 Similarly, an analysis of 21 subjects with hemophilia A who underwent major surgery with rFVIIIFc at a single center (provided through the WFH humanitarian aid program) demonstrated a lower median total factor consumption with rFVIIIFc during the surgical period than previously reported for SHL products.…”

Surgical outcomes in patients with haemophilia A or B receiving extended half‐life recombinant factor VIII and IX Fc fusion proteins: Real‐world experience in the Nordic countries

“…Data reporting real‐world experience of rFVIIIFc and rFIXFc in surgery have been published in several case reports and observational studies 16–29 . In all studies, rFVIIIFc and rFIXFc were used effectively in the peri‐operative management of HA and HB.…”

“…[10][11][12][13][14][15] Data reporting real-world experience of rFVIIIFc and rFIXFc in surgery have been published in several case reports and observational studies. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] In all studies, rFVIIIFc and rFIXFc were used effectively in the peri-operative management of HA and HB. However, details on dosage and patient outcomes were not reported consistently, and data are reported from various regions of the world with a wide range of treatment standards.…”