Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone
Open Access
- 1 October 2007
- journal article
- clinical trial
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 92 (10), 1351-1358
- https://doi.org/10.3324/haematol.11325
Abstract
Background and Objectives High-dose melphalan and autologous stem cell transplantation is currently the treatment of choice for selected patients with AL amyloidosis; however, new treatments are needed for patients who are ineligible for or relapse after this procedure. Bortezomib is a proteasome inhibitor with proven activity in multiple myeloma, and the addition of dexamethasone results in superior outcome. We evaluated the activity and feasibility of the combination of bortezomib and dexamethasone (BD) in patients with AL amyloidosis. Design and Methods Consecutive patients with histologically proven, symptomatic AL amyloidosis were treated with BD. Results Eighteen patients, including seven who had relapsed or progressed after previous therapies were treated with BD. Eleven (61%) patients had two or more organs involved; kidneys and heart were affected in 14 and 15 patients, respectively. The majority of patients had impaired performance status and high brain natriuretic peptide values; serum creatinine was elevated in six patients. Among evaluable patients, 94% had a hematologic response and 44% a hematologic complete response, including all five patients who had not responded to prior high dose dexamethasone-based treatment and one patient under dialysis. Five patients (28%) had a response in at least one affected organ. Hematologic responses were rapid (median 0.9 months) and median time to organ response was 4 months. Neurotoxicity, fatigue, peripheral edema, constipation and exacerbation of postural hypotension were manageable although necessitated dose adjustment or treatment discontinuation in 11 patients. Interpretation and Conclusions The combination of BD is feasible in patients with AL amyloidosis. Patients achieve a rapid hematologic response and toxicity can be managed with close follow-up and appropriate dose adjustment. This treatment may be a valid option for patients with severe heart or kidney impairment.Keywords
This publication has 43 references indexed in Scilit:
- Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective studyBlood, 2006
- The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosisBlood, 2006
- Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and AmyloidosisAmerican Journal of Hematology, 2005
- Bortezomib or High-Dose Dexamethasone for Relapsed Multiple MyelomaNew England Journal of Medicine, 2005
- Bortezomib in recurrent and/or refractory multiple myelomaCancer, 2005
- Risk-adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rateBone Marrow Transplantation, 2004
- Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantationBlood, 2004
- Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantationPublished by American Society of Hematology ,2004
- Poor tolerance to high doses of thalidomide in patients with primary systemic amyloidosisAmyloid, 2003
- Prognostic factors for survival and response after high‐dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: a report on 21 patientsBritish Journal of Haematology, 1998