Contributions
Abstract: PB2196
Type: Publication Only
Background
Treatment of AL amyloidosis (non IgM) currently aims at suppressing amyloidogen free light chains by targeting the underlying pathological plasmocyte clone. First line therapy relies on melphalan or bortezomib-cyclophosphamide with dexamethasone. However, there is no standardized treatment for relapsed or refractory patients. Bendamustine is an alkylating agent already used in multiple myeloma, with low cardiac, nephrologic or neurologic toxicities, and has already been studied in two series (one prospective and the other retrospective) without available data concerning organ response.
Aims
Our aim was to assess efficacy and tolerance of bendamustine as a salvage therapy in relapsed of refractory non IgM AL amyloidosis.
Methods
We retrospectively studied the data of 22 patients who received bendamustine for relapsed or refractory amyloidosis (IgA, IgG, kappa or lambda free light chain), treated in our center between 2012 and 2016. Patients had to receive at least 3 courses to be included. IgM amyloidosis were excluded. Bendamustine was administered in 28 days cycles, in association with high dose steroids. Associated treatments were determined by physicians on a case-by-case basis . Immunochemical and organ responses were assessed according to the First Roundtable on Clinical Research in Immunoglobulin Light-Chain Amyloidosis guidelines.
Results
The 22 patients (13 men, 9 women, median age 58 years) in this study had previously received a median number of 2 lines of therapy (melphalan 59%, bortezomib 86%, ASCT 9%). Organ involvement prior to therapy was as follows: heart 64%, renal 68%, liver 23%, GI tract 23%, neurologic 45%. Five patients (23%) had associated smoldering multiple myeloma. All patients received associated treatment with high dose steroids, 5 (23%) received bortezomib and 2 (9%) received thalidomide.
Twelve patients (55%) achieved haematologic response, with complete response in 1 case (5%) and VGPR in 4 cases (18%). Among patients with hematologic response, 5/12 (42%) experienced organ response. The median overall survival was 31 months. Among patients who received ulterior treatment, the median time to next treatment was 5.2 months.
Severe adverse events (grade 3 or 4) occurred in 6 patients (27%), among whom 5 experienced febrile neutropenias. One patient previously treated with melphalan, cyclophosphamide and lenalidomide developed secondary AML with complex caryotype, 3 years after 8 courses of bendamustine, of fatal evolution.
Conclusion
These results concur with those previously reported, and confirm bendamustine’s efficacy from an immunochemical point of view, resulting in organ response in 42% of cases. Immediate tolerance is good, but the potential delayed occurrence of secondary myeloid hemopathies should be taken into account, as is the case with all alkylating agents.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Amyloidosis, bendamustine, Refractory, Relapse
Abstract: PB2196
Type: Publication Only
Background
Treatment of AL amyloidosis (non IgM) currently aims at suppressing amyloidogen free light chains by targeting the underlying pathological plasmocyte clone. First line therapy relies on melphalan or bortezomib-cyclophosphamide with dexamethasone. However, there is no standardized treatment for relapsed or refractory patients. Bendamustine is an alkylating agent already used in multiple myeloma, with low cardiac, nephrologic or neurologic toxicities, and has already been studied in two series (one prospective and the other retrospective) without available data concerning organ response.
Aims
Our aim was to assess efficacy and tolerance of bendamustine as a salvage therapy in relapsed of refractory non IgM AL amyloidosis.
Methods
We retrospectively studied the data of 22 patients who received bendamustine for relapsed or refractory amyloidosis (IgA, IgG, kappa or lambda free light chain), treated in our center between 2012 and 2016. Patients had to receive at least 3 courses to be included. IgM amyloidosis were excluded. Bendamustine was administered in 28 days cycles, in association with high dose steroids. Associated treatments were determined by physicians on a case-by-case basis . Immunochemical and organ responses were assessed according to the First Roundtable on Clinical Research in Immunoglobulin Light-Chain Amyloidosis guidelines.
Results
The 22 patients (13 men, 9 women, median age 58 years) in this study had previously received a median number of 2 lines of therapy (melphalan 59%, bortezomib 86%, ASCT 9%). Organ involvement prior to therapy was as follows: heart 64%, renal 68%, liver 23%, GI tract 23%, neurologic 45%. Five patients (23%) had associated smoldering multiple myeloma. All patients received associated treatment with high dose steroids, 5 (23%) received bortezomib and 2 (9%) received thalidomide.
Twelve patients (55%) achieved haematologic response, with complete response in 1 case (5%) and VGPR in 4 cases (18%). Among patients with hematologic response, 5/12 (42%) experienced organ response. The median overall survival was 31 months. Among patients who received ulterior treatment, the median time to next treatment was 5.2 months.
Severe adverse events (grade 3 or 4) occurred in 6 patients (27%), among whom 5 experienced febrile neutropenias. One patient previously treated with melphalan, cyclophosphamide and lenalidomide developed secondary AML with complex caryotype, 3 years after 8 courses of bendamustine, of fatal evolution.
Conclusion
These results concur with those previously reported, and confirm bendamustine’s efficacy from an immunochemical point of view, resulting in organ response in 42% of cases. Immediate tolerance is good, but the potential delayed occurrence of secondary myeloid hemopathies should be taken into account, as is the case with all alkylating agents.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Amyloidosis, bendamustine, Refractory, Relapse