A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis

Abstract

Key Points CyBorD achieves excellent outcome in noncardiac patients with AL amyloidosis and can rescue subjects with reversible heart damage. The outcome of high-risk patients remains poor, but response to CyBorD can also improve survival in this group.

Recovery from LCDD-associated Severe Liver Cholestasis: a Case Report and Literature Review

“…Chemotherapeutic regimens containing the proteasome inhibitor bortezomib have shown efficacy and good tolerance profile in both AL amyloidosis [26][27][28] and Randall-type MIDD [25] but their effect on the clearance of LC tissular deposits, although possibly accepted, remains to be demonstrated. Interestingly, Komatsuda et al [29] reported the disappearance of nodular mesangial lesions and disappearance of kappa light chain deposits in a patient with kidney LCDD under longterm chemotherapy.…”

Addition of Cyclophosphamide and Higher Doses of Dexamethasone Do Not Improve Outcomes of Patients With AL amyloidosis Treated With Bortezomib

“…Nonetheless, hematologic response rates in our patients are very similar to those reported in larger collaborative series. 9 Higher doses of cyclophosphamide could probably be more effective, as in the EVOLUTION study, but at the expense of increased toxicity. 25 Recent data indicate that patients bearing plasma cell clones with certain cytogenetic abnormalities may have a less favorable outcome with bortezomib-based therapies; 26 however, cytogenetics were available only in a small number of patients, thus we cannot make statistically meaningful comparisons.…”

“…24 Another important question concerns the dose of cyclophosphamide, which is lower than what is commonly used in myeloma patients. Such moderate doses are commonly used in most centers, [8][9][10] although some physicians prefer to use oral rather than the intravenous route, which may affect pharmacodynamics and pharmacokinetics of cyclophosphamide as this drug needs to be activated in the liver. Nonetheless, hematologic response rates in our patients are very similar to those reported in larger collaborative series.…”

“…4 Bortezomib is a very effective drug in targeting plasma cells and can rapidly induce plasma cell apoptosis. In the clinical setting, several lines of data have shown that bortezomib either as single agent 5 or in combinations, with dexamethasone (VD) 6,7 or with the addition of cyclophosphamide (VCD), [8][9][10] induces high rates of hematologic complete responses and organ responses. Dexamethasone has rapid antiplasma cell activity and pulsed dexamethasone 11 or concomitantly with alkylating agents 12 or bortezomib is commonly used.…”

Outcomes of autologous hematopoietic cell transplantation in primary amyloidosis after bortezomib-based induction therapy

“…3,4 Bortezomib is a proteasome inhibitor with activity in plasma cell disorders that has been reported to achieve high rates of hematologic and organ response in amyloidosis. 5,6 Treatment with bortezomib pre-AHCT has been shown to improve transplant eligibility for patients, previously considered to be too high risk for AHCT, and may increase the response rates following AHCT. [7][8][9][10] Herein, we describe our experience using bortezomib prior to AHCT and demonstrate the feasibility of this approach.…”