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

The combination of cyclophosphamide/bortezomib/dexamethasone (CyBorD) showed early promise of high rates of hematologic responses tempered by studies showing the inability to overcome poor prognosis of advanced cardiac amyloidosis. Large studies are needed to clarify its role in light chain (AL) amyloidosis. We report the outcome of 230 patients treated frontline with CyBorD. Overall hematologic response rate was 60%, and in the 201 patients with measurable disease it was 62%, with 43% achieving at least very good partial response (VGPR). Cardiac response was reached in 17% of patients and renal response in 25% of patients. Advanced cardiac stage III patients (amino-terminal pro-natriuretic peptide type B >8500 ng/L) had lower response rates (42%, ≥ VGPR 23%) and poorer survival (median, 7 months). Nevertheless, hematologic response improved survival in these subjects (67% at 2 years), showing the importance of striving for a good response even in this group.

[1]  A. Foli,et al.  A practical approach to the diagnosis of systemic amyloidoses. , 2015, Blood.

[2]  M. Dimopoulos,et al.  A Randomized Phase III Trial of Melphalan and Dexamethasone (MDex) versus Bortezomib, Melphalan and Dexamethasone (BMDex) for Untreated Patients with AL Amyloidosis , 2014 .

[3]  P. Hawkins,et al.  A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis , 2014, Leukemia.

[4]  A. Foli,et al.  Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients , 2014, Leukemia.

[5]  D. Esseltine,et al.  Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. , 2014, Blood.

[6]  A. Foli,et al.  A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. , 2014, Blood.

[7]  P. Hari,et al.  Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naïve patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III) , 2014, Haematologica.

[8]  C. Whelan,et al.  CHARACTERISTICS AND OUTCOMES OF 714 PATIENTS WITH SYSTEMIC AL AMYLOIDOSIS -ANALYSIS OF A PROSPECTIVE OBSERVATIONAL STUDY (ALCHEMY STUDY) , 2014 .

[9]  A. Foli,et al.  Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach , 2014, Haematologica.

[10]  Giampaolo Merlini,et al.  Shotgun protein profile of human adipose tissue and its changes in relation to systemic amyloidoses. , 2013, Journal of proteome research.

[11]  G. Merlini,et al.  Systemic light chain amyloidosis: an update for treating physicians. , 2013, Blood.

[12]  M. Dimopoulos,et al.  A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. , 2013, Blood.

[13]  M. Dimopoulos,et al.  New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  P. L. Bergsagel,et al.  Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. , 2012, Blood.

[15]  P. Hawkins,et al.  Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. , 2011, Blood.

[16]  M. Dimopoulos,et al.  Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  D. Reece,et al.  Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. , 2009, Blood.

[18]  K. Anderson,et al.  The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition. , 2009, Blood.

[19]  G. Merlini,et al.  Bortezomib in the treatment of AL amyloidosis: targeted therapy? , 2007, Haematologica.

[20]  P. Hawkins,et al.  Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. , 2007, Blood.

[21]  T. Therneau,et al.  Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  D. Booth,et al.  Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. , 2002, The New England journal of medicine.

[23]  A. Foli,et al.  Salvage therapy with lenalidomide and dexamethasone in patients with advanced AL amyloidosis refractory to melphalan, bortezomib, and thalidomide , 2011, Annals of Hematology.