RENAL AND HEMATOLOGIC OUTCOMES OF BORTEZOMIB-BASED TREATMENT IN PATIENTS WITH LIGHT CHAIN DEPOSITION DISEASE
(Abstract release date: 05/19/16)
EHA Library. Kastritis E. 06/09/16; 132843; E1294
Dr. Efstathios Kastritis
Contributions
Contributions
Abstract
Abstract: E1294
Type: Eposter Presentation
Background
Light chain deposition disease (LCDD) is characterized by amorphous deposits of monotypic immunoglobulin light chains in the kidneys leading inevitably to end-stage renal disease (ESRD) if untreated. LCDD is one of the recently defined monoglonal gammopathies of renal significance (MGRS) and less often is associated with an underlying symptomatic myeloma. However, no optimal treatment or response criteria for the evaluation of treatment outcomes have been established although bortezomib-based regimens have been recommended based on small patient series.
Aims
to evaluate the outcomes of LCDD after bortezomib-based treatment, the prognostic effect of clinicopathological characteristics and the impact of hematologic response to renal survival.
Methods
18 consecutive patients with renal biopsy-proven LCDD who received primary therapy with bortezomib were included in the analysis.
Results
by IF all biopsies had linear staining exclusively for κ or λ chains along the TBM and/or GBM; other findings included interstitial fibrosis (78%), mesangial expansion/proliferation (72%), tubular atrophy (67%) and nodular mesangial sclerosis (56%). Median age was 65.5 (range: 46-85) years and 10(55%) patients were >65 years; 89% presented with hypertension, median 24h proteinuria was 3.3 gr (range 0.4-10.2), 13/18 patients had eGFR<60 ml/min and 9/18 (50%) had eGFR<30ml/min. Fourteen patients (78%) had measurable FLCs (dFLC≥50mg/l and abnormal ratio). Median bone marrow infiltration was 15% but no patient had symptomatic MM by the CRAB criteria. Bortezomib with dexamethasone (VD) was given in 12/18(67%) and VD plus cyclophosphamide (VCD) in 6/18 (33%) patients for a median of 4 cycles; 10/18(56%) received bortezomib SC. Among evaluable patients 11/14(79%) had a hematologic response (PR, VGPR or CR), including 5(36%) with CR, 1(7%) with VGPR and 5(36%) with PR. At the time of diagnosis or during follow-up, 6/18 (33%) patients progressed to ESRD. Three of the 9 patients improved their eGFR from <15 to 15-29ml/min and 3 patients from 15-29 to 30-59ml/min while 9/18 patients achieved a 50% reduction of proteinuria. Improvement in eGFR was observed only in patients (6 /14) who achieved a hematologic CR or VGPR, and no patient who achieved a VGPR or CR developed ESRD. In contrast, 5/8 patients who achieved a PR or less progressed to ESRD (P=0.031). Improvement of proteinuria was observed in all patients who achieved a CR and in 2/9 patients who achieved a hematologic PR. In univariate analysis baseline eGFR<30ml/min was associated with increased risk for ESRD (OR=8.75, p=0.086); no pathology feature was associated with renal response or risk of ESRD. Median follow-up is 39 months and 13/18 patients remain alive; only 3 (17%) had a hematologic relapse/progression. Two patients died on dialysis and median survival from initiation of dialysis was 5 (range:1-13) months. Three patients received ASCT as consolidation after bortezomib induction. Bortezomib-related peripheral neuropathy occurred in 67% (grade 2 in 7 and grade 3 in 2 patients); in 9/18 patients a dose reduction of bortezomib was required but no patient discontinued bortezomib due to neuropathy. Neuropathy grade ≥2 occurred in 7/8(87.5%) vs 2/10(20%) patients who received IV vs SC bortezomib (P=0.041).
Conclusion
bortezomib-based treatment is active and safe for patients with LCDD but at least a hematologic VGPR is required in order to improve renal prognosis. Prospective studies are needed to determine the optimal management for LCDD and identify further predictors for renal prognosis.
Session topic: E-poster
Keyword(s): Bortezomib, Monoclonal gammopathy, Renal impairment
Type: Eposter Presentation
Background
Light chain deposition disease (LCDD) is characterized by amorphous deposits of monotypic immunoglobulin light chains in the kidneys leading inevitably to end-stage renal disease (ESRD) if untreated. LCDD is one of the recently defined monoglonal gammopathies of renal significance (MGRS) and less often is associated with an underlying symptomatic myeloma. However, no optimal treatment or response criteria for the evaluation of treatment outcomes have been established although bortezomib-based regimens have been recommended based on small patient series.
Aims
to evaluate the outcomes of LCDD after bortezomib-based treatment, the prognostic effect of clinicopathological characteristics and the impact of hematologic response to renal survival.
Methods
18 consecutive patients with renal biopsy-proven LCDD who received primary therapy with bortezomib were included in the analysis.
Results
by IF all biopsies had linear staining exclusively for κ or λ chains along the TBM and/or GBM; other findings included interstitial fibrosis (78%), mesangial expansion/proliferation (72%), tubular atrophy (67%) and nodular mesangial sclerosis (56%). Median age was 65.5 (range: 46-85) years and 10(55%) patients were >65 years; 89% presented with hypertension, median 24h proteinuria was 3.3 gr (range 0.4-10.2), 13/18 patients had eGFR<60 ml/min and 9/18 (50%) had eGFR<30ml/min. Fourteen patients (78%) had measurable FLCs (dFLC≥50mg/l and abnormal ratio). Median bone marrow infiltration was 15% but no patient had symptomatic MM by the CRAB criteria. Bortezomib with dexamethasone (VD) was given in 12/18(67%) and VD plus cyclophosphamide (VCD) in 6/18 (33%) patients for a median of 4 cycles; 10/18(56%) received bortezomib SC. Among evaluable patients 11/14(79%) had a hematologic response (PR, VGPR or CR), including 5(36%) with CR, 1(7%) with VGPR and 5(36%) with PR. At the time of diagnosis or during follow-up, 6/18 (33%) patients progressed to ESRD. Three of the 9 patients improved their eGFR from <15 to 15-29ml/min and 3 patients from 15-29 to 30-59ml/min while 9/18 patients achieved a 50% reduction of proteinuria. Improvement in eGFR was observed only in patients (6 /14) who achieved a hematologic CR or VGPR, and no patient who achieved a VGPR or CR developed ESRD. In contrast, 5/8 patients who achieved a PR or less progressed to ESRD (P=0.031). Improvement of proteinuria was observed in all patients who achieved a CR and in 2/9 patients who achieved a hematologic PR. In univariate analysis baseline eGFR<30ml/min was associated with increased risk for ESRD (OR=8.75, p=0.086); no pathology feature was associated with renal response or risk of ESRD. Median follow-up is 39 months and 13/18 patients remain alive; only 3 (17%) had a hematologic relapse/progression. Two patients died on dialysis and median survival from initiation of dialysis was 5 (range:1-13) months. Three patients received ASCT as consolidation after bortezomib induction. Bortezomib-related peripheral neuropathy occurred in 67% (grade 2 in 7 and grade 3 in 2 patients); in 9/18 patients a dose reduction of bortezomib was required but no patient discontinued bortezomib due to neuropathy. Neuropathy grade ≥2 occurred in 7/8(87.5%) vs 2/10(20%) patients who received IV vs SC bortezomib (P=0.041).
Conclusion
bortezomib-based treatment is active and safe for patients with LCDD but at least a hematologic VGPR is required in order to improve renal prognosis. Prospective studies are needed to determine the optimal management for LCDD and identify further predictors for renal prognosis.
Session topic: E-poster
Keyword(s): Bortezomib, Monoclonal gammopathy, Renal impairment
Abstract: E1294
Type: Eposter Presentation
Background
Light chain deposition disease (LCDD) is characterized by amorphous deposits of monotypic immunoglobulin light chains in the kidneys leading inevitably to end-stage renal disease (ESRD) if untreated. LCDD is one of the recently defined monoglonal gammopathies of renal significance (MGRS) and less often is associated with an underlying symptomatic myeloma. However, no optimal treatment or response criteria for the evaluation of treatment outcomes have been established although bortezomib-based regimens have been recommended based on small patient series.
Aims
to evaluate the outcomes of LCDD after bortezomib-based treatment, the prognostic effect of clinicopathological characteristics and the impact of hematologic response to renal survival.
Methods
18 consecutive patients with renal biopsy-proven LCDD who received primary therapy with bortezomib were included in the analysis.
Results
by IF all biopsies had linear staining exclusively for κ or λ chains along the TBM and/or GBM; other findings included interstitial fibrosis (78%), mesangial expansion/proliferation (72%), tubular atrophy (67%) and nodular mesangial sclerosis (56%). Median age was 65.5 (range: 46-85) years and 10(55%) patients were >65 years; 89% presented with hypertension, median 24h proteinuria was 3.3 gr (range 0.4-10.2), 13/18 patients had eGFR<60 ml/min and 9/18 (50%) had eGFR<30ml/min. Fourteen patients (78%) had measurable FLCs (dFLC≥50mg/l and abnormal ratio). Median bone marrow infiltration was 15% but no patient had symptomatic MM by the CRAB criteria. Bortezomib with dexamethasone (VD) was given in 12/18(67%) and VD plus cyclophosphamide (VCD) in 6/18 (33%) patients for a median of 4 cycles; 10/18(56%) received bortezomib SC. Among evaluable patients 11/14(79%) had a hematologic response (PR, VGPR or CR), including 5(36%) with CR, 1(7%) with VGPR and 5(36%) with PR. At the time of diagnosis or during follow-up, 6/18 (33%) patients progressed to ESRD. Three of the 9 patients improved their eGFR from <15 to 15-29ml/min and 3 patients from 15-29 to 30-59ml/min while 9/18 patients achieved a 50% reduction of proteinuria. Improvement in eGFR was observed only in patients (6 /14) who achieved a hematologic CR or VGPR, and no patient who achieved a VGPR or CR developed ESRD. In contrast, 5/8 patients who achieved a PR or less progressed to ESRD (P=0.031). Improvement of proteinuria was observed in all patients who achieved a CR and in 2/9 patients who achieved a hematologic PR. In univariate analysis baseline eGFR<30ml/min was associated with increased risk for ESRD (OR=8.75, p=0.086); no pathology feature was associated with renal response or risk of ESRD. Median follow-up is 39 months and 13/18 patients remain alive; only 3 (17%) had a hematologic relapse/progression. Two patients died on dialysis and median survival from initiation of dialysis was 5 (range:1-13) months. Three patients received ASCT as consolidation after bortezomib induction. Bortezomib-related peripheral neuropathy occurred in 67% (grade 2 in 7 and grade 3 in 2 patients); in 9/18 patients a dose reduction of bortezomib was required but no patient discontinued bortezomib due to neuropathy. Neuropathy grade ≥2 occurred in 7/8(87.5%) vs 2/10(20%) patients who received IV vs SC bortezomib (P=0.041).
Conclusion
bortezomib-based treatment is active and safe for patients with LCDD but at least a hematologic VGPR is required in order to improve renal prognosis. Prospective studies are needed to determine the optimal management for LCDD and identify further predictors for renal prognosis.
Session topic: E-poster
Keyword(s): Bortezomib, Monoclonal gammopathy, Renal impairment
Type: Eposter Presentation
Background
Light chain deposition disease (LCDD) is characterized by amorphous deposits of monotypic immunoglobulin light chains in the kidneys leading inevitably to end-stage renal disease (ESRD) if untreated. LCDD is one of the recently defined monoglonal gammopathies of renal significance (MGRS) and less often is associated with an underlying symptomatic myeloma. However, no optimal treatment or response criteria for the evaluation of treatment outcomes have been established although bortezomib-based regimens have been recommended based on small patient series.
Aims
to evaluate the outcomes of LCDD after bortezomib-based treatment, the prognostic effect of clinicopathological characteristics and the impact of hematologic response to renal survival.
Methods
18 consecutive patients with renal biopsy-proven LCDD who received primary therapy with bortezomib were included in the analysis.
Results
by IF all biopsies had linear staining exclusively for κ or λ chains along the TBM and/or GBM; other findings included interstitial fibrosis (78%), mesangial expansion/proliferation (72%), tubular atrophy (67%) and nodular mesangial sclerosis (56%). Median age was 65.5 (range: 46-85) years and 10(55%) patients were >65 years; 89% presented with hypertension, median 24h proteinuria was 3.3 gr (range 0.4-10.2), 13/18 patients had eGFR<60 ml/min and 9/18 (50%) had eGFR<30ml/min. Fourteen patients (78%) had measurable FLCs (dFLC≥50mg/l and abnormal ratio). Median bone marrow infiltration was 15% but no patient had symptomatic MM by the CRAB criteria. Bortezomib with dexamethasone (VD) was given in 12/18(67%) and VD plus cyclophosphamide (VCD) in 6/18 (33%) patients for a median of 4 cycles; 10/18(56%) received bortezomib SC. Among evaluable patients 11/14(79%) had a hematologic response (PR, VGPR or CR), including 5(36%) with CR, 1(7%) with VGPR and 5(36%) with PR. At the time of diagnosis or during follow-up, 6/18 (33%) patients progressed to ESRD. Three of the 9 patients improved their eGFR from <15 to 15-29ml/min and 3 patients from 15-29 to 30-59ml/min while 9/18 patients achieved a 50% reduction of proteinuria. Improvement in eGFR was observed only in patients (6 /14) who achieved a hematologic CR or VGPR, and no patient who achieved a VGPR or CR developed ESRD. In contrast, 5/8 patients who achieved a PR or less progressed to ESRD (P=0.031). Improvement of proteinuria was observed in all patients who achieved a CR and in 2/9 patients who achieved a hematologic PR. In univariate analysis baseline eGFR<30ml/min was associated with increased risk for ESRD (OR=8.75, p=0.086); no pathology feature was associated with renal response or risk of ESRD. Median follow-up is 39 months and 13/18 patients remain alive; only 3 (17%) had a hematologic relapse/progression. Two patients died on dialysis and median survival from initiation of dialysis was 5 (range:1-13) months. Three patients received ASCT as consolidation after bortezomib induction. Bortezomib-related peripheral neuropathy occurred in 67% (grade 2 in 7 and grade 3 in 2 patients); in 9/18 patients a dose reduction of bortezomib was required but no patient discontinued bortezomib due to neuropathy. Neuropathy grade ≥2 occurred in 7/8(87.5%) vs 2/10(20%) patients who received IV vs SC bortezomib (P=0.041).
Conclusion
bortezomib-based treatment is active and safe for patients with LCDD but at least a hematologic VGPR is required in order to improve renal prognosis. Prospective studies are needed to determine the optimal management for LCDD and identify further predictors for renal prognosis.
Session topic: E-poster
Keyword(s): Bortezomib, Monoclonal gammopathy, Renal impairment
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