Abstract
Preliminary data suggest a positive effect of taliglucerase alfa on the bone marrow infiltration of Gaucher cells. In this investigator-initiated study, we report the impact of taliglucerase alfa on the bone marrow fat fraction (FF) in 26 patients assessed by quantitative chemical shift imaging (QCSI). Of 15 treatment-naïve patients (median age 48 [range 24–68] years), eight had baseline FF ≤ 0.3, six of those with a FF ≤ 0.23 (‘bone at risk’). All significantly improved from a median baseline FF of 0.24 (0.15–0.32) to 1st year FF of 0.37 (0.25–0.54) and 2nd year FF of 0.42 (0.27–0.59) (p = 0.01). Among the 11 ‘switch-over’ patients (median age 42 [range 33–69] years; median imiglucerase exposure 8 [range 1–17] years), eight had baseline FF ≤ 0.3, five of those with FF < 0.23. All, but one, significantly improved from a median baseline FF of 0.17 (0.08–0.28) to 1st year FF of 0.3 (0.05–0.34) and 2nd year FF of 0.34 (0.08–0.44) (p = 0.03). Two elderly female patients (age 43 and 58 years, with 17 years imiglucerase exposure) who remained at the same enzyme replacement therapy dose, increased from baseline FF of 0.13 and 0.19 to 0.26 at 1 year. Although the number of observations is small, we hypothesize that switching to taliglucerase may result in an improved bone marrow response. A larger study is needed to assess the early benefit of taliglucerase alfa in adult patients with type 1 Gaucher disease on the bone marrow compartment.
Highlights
Gaucher disease (GD), one of the most prevalent lysosomal storage disorder, results from defective β-glucocerebrosidase production and subsequent accumulation of glucocerebroside in macrophages (Zimran and Elstein 2016)
In 2012, we reported improvement in quantitative chemical shift imaging (QCSI) in a sub-group of eight patients from the pivotal taliglucerase alfa clinical trial, who were willing to travel to the Academic Medical Center (AMC) in Amsterdam to undergo periodic QCSI studies
Comparable data at 9 months of therapy have not been reported for treatment with imiglucerase or velaglucerase alfa, we hypothesized that taliglucerase had a more specific beneficial effect on bone marrow involvement, and we initiated a study to assess the bone marrow response to taliglucerase alfa using the same methodology of QCSI in a larger, new cohort of adult patients with GD, both treatment-naïve to Enzyme replacement therapy (ERT) and those switched from imiglucerase, who received taliglucerase alfa during the 3 years of approved early access programs (EAP) in Israel
Summary
Gaucher disease (GD), one of the most prevalent lysosomal storage disorder, results from defective β-glucocerebrosidase production and subsequent accumulation of glucocerebroside in macrophages (Zimran and Elstein 2016). In 2012, we reported improvement in QCSI in a sub-group of eight patients from the pivotal taliglucerase alfa clinical trial, who were willing to travel to the AMC in Amsterdam to undergo periodic QCSI studies (van Dussen et al 2013). In this small cohort of patients treated with either 30 or 60 units/kg every other week (EOW), a significant increase in lumbar spine FF was shown, reflecting the clearance of Gaucher cells from the bone marrow. Comparable data at 9 months of therapy have not been reported for treatment with imiglucerase or velaglucerase alfa, we hypothesized that taliglucerase had a more specific beneficial effect on bone marrow involvement, and we initiated a study to assess the bone marrow response to taliglucerase alfa using the same methodology of QCSI in a larger, new cohort of adult patients with GD, both treatment-naïve to ERT and those switched from imiglucerase, who received taliglucerase alfa during the 3 years of approved early access programs (EAP) in Israel
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