Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib

M Gavriatopoulou,D C Ziogas,E Papadopoulou,M A Dimopoulos,E Kastritis,C Pamboucas,E Terpos,H Gakiopoulou,E Psimenou,I Panagiotidis,D Fotiou,M Roussou,S Giannouli,N Kanellias,A Ntalianis,M Migkou,A Tasidou,E Manios,E Eleutherakis-Papaiakovou

doi:10.1038/bcj.2017.47

M Gavriatopoulou, D C Ziogas + Show 17 more

Open Access

https://doi.org/10.1038/bcj.2017.47

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Abstract

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Highlights

Treatment of amyloid light-chain (AL) amyloidosis is based on the elimination of the plasma cell clone that produces the amyloidogenic light chains.[1]
Bortezomib was given in 41% of patients who received VD and in 40% of those treated with VCD
Higher doses of dexamethasone or twice-weekly bortezomib schedule were not associated with significantly higher hematologic response rates or complete response (CR)+very good partial response (VGPR) rates: 46% vs 36% of patients

Summary

Introduction

Treatment of amyloid light-chain (AL) amyloidosis is based on the elimination of the plasma cell clone that produces the amyloidogenic light chains.[1]. The aim of this analysis was to compare the outcomes of patients with AL amyloidosis who have received primary therapy with VD to that of patients who received VCD to evaluate the incremental value of the addition of cyclophosphamide to VD and the role of dexamethasone doses.

Results

Conclusion