Improvement in bone marrow infiltration in patients with type I Gaucher disease treated with taliglucerase alfa

Ari Zimran, Tama Dinur, Shoshana Revel-Vilk, Eric M Akkerman, Laura van Dussen, Carla E M Hollak, Hannah Maayan, Gheona Altarescu, Raul Chertkoff, Mario Maas, Ari Zimran, Tama Dinur, Shoshana Revel-Vilk, Eric M Akkerman, Laura van Dussen, Carla E M Hollak, Hannah Maayan, Gheona Altarescu, Raul Chertkoff, Mario Maas

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.

Keywords: Bone response; Enzyme replacement therapy; Gaucher disease; Quantitative chemical shift imaging; Taliglucerase alfa.

Conflict of interest statement

The costs of the travel to AMC (including flights, accommodations, and meals) and for the performance of the QCSI were provided as a grant by Protalix Biotherapeutics.

Ari Zimran received consultancy fees and was a member of the Protalix Biotherapeutics scientific Advisory Board at the time of the study. Ari Zimran receives honoraria from Shire, Pfizer and Sanofi/Genzyme. The SZMC Gaucher Clinic receives support from Sanofi/Genzyme for participation in the ICGG Registry, from Shire for the GOS Registry, and from Pfizer for TALIAS. The Clinic also receives research grants from Shire and from Pfizer.

Tama Dinur declares that she has no conflict of interest.

Shoshana Revel-Vilk receives honoraria, travel fee and research support from Pfizer, Sanofi-Genzyme and Shire.

Eric M. Akkerman declares that he has no conflict of interest.

Laura van Dussen declares that she has no conflict of interest.

Carla E. M. Hollak is involved in pre-marketing studies with Genzyme, Protalix and Idorsia. Financial arrangements are made through AMC Research BV. No fees, travel support or grants are obtained from the Pharmaceutical industry.

Hannah Maayan declares that she has no conflict of interest.

Gheona Altarescu receives honoraria from Pfizer, Sanofi-Genzyme and Shire.

Raul Chertkoff is an employee of Protalix Biotherapeutics.

Mario Maas is involved in studies with Sanofi, Protalix. Financial arrangements are made through AMC Research BV and are beneficial for the hospital, no private funding. No fees, travel support or grants are obtained from the Pharmaceutical industry. He also is deputy editor of European Journal of Radiology.

Figures

Fig. 1
Fig. 1
Patient disposition in the Early Access Program. *Two patients with lumbar spine fat fraction (FF) >0.30 were followed via quantitative chemical shift imaging (QCSI) (one due to severe osteoporosis and the other with very severe phenotype at baseline). †Not followed with QCSI because baseline FF was >0.30
Fig. 2
Fig. 2
a Quantitative chemical shift imaging (QSCI) findings from treatment-naïve patients with lumbar spine fat fraction (FF) ≤0.30 at baseline. b Quantitative chemical shift imaging (QSCI) findings from treatment-switch patients who remained at the same dose

References

    1. Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med. 1991;324:1464–1470. doi: 10.1056/NEJM199105233242104.
    1. de Fost M, Hollak CE, Groener JE, et al. Superior effects of high-dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2-center retrospective analysis. Blood. 2006;108:830–835. doi: 10.1182/blood-2005-12-5072.
    1. Elstein D, Haims AH, Zahrieh D, Cohn GM, Zimran A. Impact of velaglucerase alfa on bone marrow burden score in adult patients with type 1 Gaucher disease: 7-year follow-up. Blood Cells Mol Dis. 2014;53:56–60. doi: 10.1016/j.bcmd.2014.02.006.
    1. Grabowski GA, Golembo M, Shaaltiel Y. Taliglucerase alfa: an enzyme replacement therapy using plant cell expression technology. Mol Genet Metab. 2014;112:1–8. doi: 10.1016/j.ymgme.2014.02.011.
    1. Hollak C, Maas M, Akkerman E, den Heeten A, Aerts H. Dixon quantitative chemical shift imaging is a sensitive tool for the evaluation of bone marrow responses to individualized doses of enzyme supplementation therapy in type 1 Gaucher disease. Blood Cells Mol Dis. 2001;27:1005–1012. doi: 10.1006/bcmd.2001.0474.
    1. Lebel E, Dweck A, Foldes AJ, et al. Bone density changes with enzyme therapy for Gaucher disease. J Bone Miner Metab. 2004;22:597–601. doi: 10.1007/s00774-004-0529-8.
    1. Maas M, Akkerman EM, Venema HW, Stoker J, Den Heeten GJ. Dixon quantitative chemical shift MRI for bone marrow evaluation in the lumbar spine: a reproducibility study in healthy volunteers. J Comput Assist Tomogr. 2001;25:691–697. doi: 10.1097/00004728-200109000-00005.
    1. Maas M, Hollak CE, Akkerman EM, Aerts JM, Stoker J, Den Heeten GJ. Quantification of skeletal involvement in adults with type I Gaucher's disease: fat fraction measured by Dixon quantitative chemical shift imaging as a valid parameter. AJR Am J Roentgenol. 2002;179:961–965. doi: 10.2214/ajr.179.4.1790961.
    1. Maas M, van Kuijk C, Stoker J, et al. Quantification of bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative to Dixon quantitative chemical shift MR imaging--initial experience. Radiology. 2003;229:554–561. doi: 10.1148/radiol.2292020296.
    1. Pastores GM, Petakov M, Giraldo P, et al. A phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase. Blood Cells Mol Dis. 2014;53:253–260. doi: 10.1016/j.bcmd.2014.05.004.
    1. Rosenthal DI, Doppelt SH, Mankin HJ, et al. Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics. 1995;96:629–637.
    1. Shemesh E, Deroma L, Bembi B, et al (2015) Enzyme replacement and substrate reduction therapy for Gaucher disease. Cochrane Database Syst Rev 3:CD010324
    1. Stirnemann J, Belmatoug N, Camou F, et al. A review of Gaucher disease pathophysiology, clinical presentation and treatments. Int J Mol Sci. 2017;18:441. doi: 10.3390/ijms18020441.
    1. Tekoah Y, Shulman A, Kizhner T, et al. Large-scale production of pharmaceutical proteins in plant cell culture-the Protalix experience. Plant Biotechnol J. 2015;13:1199–1208. doi: 10.1111/pbi.12428.
    1. van Dussen L, Akkerman EM, Hollak CE, Nederveen AJ, Maas M. Evaluation of an imaging biomarker, Dixon quantitative chemical shift imaging, in Gaucher disease: lessons learned. J Inherit Metab Dis. 2014;37:1003–1011. doi: 10.1007/s10545-014-9726-3.
    1. van Dussen L, Zimran A, Akkerman EM, et al. Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease. Blood Cells Mol Dis. 2013;50:206–211. doi: 10.1016/j.bcmd.2012.11.001.
    1. Weinreb NJ, Charrow J, Andersson HC, et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher registry. Am J Med. 2002;113:112–119. doi: 10.1016/S0002-9343(02)01150-6.
    1. Wenstrup RJ, Kacena KA, Kaplan P, et al. Effect of enzyme replacement therapy with imiglucerase on BMD in type 1 Gaucher disease. J Bone Miner Res. 2007;22:119–126. doi: 10.1359/jbmr.061004.
    1. Zimran A, Brill-Almon E, Chertkoff R, et al. Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood. 2011;118:5767–5773. doi: 10.1182/blood-2011-07-366955.
    1. Zimran A, Duran G, Mehta A, et al. Long-term efficacy and safety results of taliglucerase alfa up to 36 months in adult treatment-naive patients with Gaucher disease. Am J Hematol. 2016;91:656–660. doi: 10.1002/ajh.24369.
    1. Zimran A, Elstein D. Management of Gaucher disease: enzyme replacement therapy. Pediatr Endocrinol Rev. 2014;12(Suppl 1):82–87.
    1. Zimran A, Elstein D. Gaucher disease and related lysosomal storage diseases. In: Kaushansky K, Lichtman M, Beutler E, Kipps TJ, Seligsohn U, Prchal J, editors. Williams’ hematology. New-York: McGraw-Hill; 2016.
    1. Zimran A, Gonzalez-Rodriguez DE, Abrahamov A, et al. Safety and efficacy of two dose levels of taliglucerase alfa in pediatric patients with Gaucher disease. Blood Cells Mol Dis. 2015;54:9–16. doi: 10.1016/j.bcmd.2014.10.002.

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