Impact of velaglucerase alfa on bone marrow burden score in adult patients with type 1 Gaucher disease: 7-Year follow-up

Background: Bone marrow infiltration by substrate-engorged "Gaucher" cells manifests early in Gaucher disease (GD). The impact of velaglucerase alfa on bone marrow burden (BMB) was evaluated as an exploratory assessment. Methods: BMB scores were assessed using T1- and T2-weighted magnetic resonance images of the lumbar spine (LS) and femora among symptomatic GD patients who participated in the 9-month Phase I/II trial and long-term extension study for velaglucerase alfa. A post-hoc assessment of marrow involvement was performed. BMB scores per site are 0-8 (0/1 = normal; 8 = severe infiltration). Results: The median LS-BMB score at baseline was 6 (n = 12; range 3-8); at 9. months, compared with baseline, there was a median change of - 2 (n = 11; two-sided p-value = 0.0078). LS-BMB scores continued to decrease through 5. years (n = 8; median change from baseline - 5 [p = 0.0078], median score 1 [range 1-4]) and were subsequently sustained through 7. years (n = 8). LS-BMB decreases of ≥ 2 points occurred in 6/11 patients at 9. months, and in all assessable patients (8/8) by 5. years. Long-term femoral BMB (F-BMB) assessment was possible for three patients; all experienced reductions of ≥ 2 points at 5. years with a total score (LS-BMB. +. F-BMB) decrease ≥ 4. Conclusions: This post hoc analysis suggests improvement in BMB scores through 5. years that was sustained through 7. years, despite dose reduction from 15. months. Prospective studies in a large cohort are needed to validate these findings.