Abstract

Abstract 5027

Background:

LCDD is a rare plasma cell dyscrasia characterized by deposition of immunoglobulin light chain in kidneys and, occasionally, in other organs such as liver and heart. Most patients present with rapidly deteriorating renal function and nephrotic proteinuria.

There is no standard treatment for LCDD. High dose dexametasone (HDD) with or without alkylating agents and high dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) have been used, the latter with better results. Recently the combination therapy with Bortezomib-Dexametasone (BD) has been used in small series of patients and has shown promising results. Here we report on four patients with LCDD treated in our center from September 2010 to September 2011 with BD as induction therapy.

Patients and Methods:

The characteristics of the patients are shown in Table 1. Three patients were male; the median age was 44. 5 years (range 37–64 years). Two patients had more than 20% bone marrow plasma cell count with no evidence of active multiple myeloma (MM) defined by osteolytic bone disease, hypercalcemia or myeloma cast nephropaty. All patients had renal biopsy with histologic and immunofluorescence studies. In all patients except one, the diagnosis was confirmed by electron microscopy examination. One patient was therapy naive and three patients were refractory to HDD. All patients but one presented with impaired renal function and all of them showed nephrotic albuminuria. Serum free light chains values (sFLC) were high in all patients, with abnormal kappa to lambda ratio (R k/λ). Noteworthy, in three patients serum immunofixation electrophoresis did not succeed in detecting the circulating monoclonal light chain. Patients were given Bortezomib (1. 3 mg/m2days 1, 4, 8 and 11) and Dexamethasone (40 mg days 1–4) every 21 days, for three to six cycles.

Results:

Two patients achieved normalization of R k/λ. One patient achieved reduction of more than 50% of involved sFLC and reduction of more than 50% of the M protein after three cycles. One patient had progressive disease. None of the responding patients with renal impairment achieved improvement of the renal function, but all responding patients showed reduction of more than 50% of initial albuminuria. After BD one patient achieved hematological CR, one VGPR and one PR (Gertz MA et al., Amyloid 2010). All responding patients were eligible for ASCT. Two patients underwent stem cell mobilization with cyclophosphamide 4 g/m2; one patient was mobilized with G-CSF alone. Melphalan dose was reduced to 140 mg/m2in the only patient undergoing hemodyalisis. There were no complications related to stem cell harvest and engraftment (only one patient showed a late platelet engraftment). After ASCT two patients achieved at least VGPR; one patient achieved a PR and he underwent second ASCT achieving again a PR. Dose reduction of Bortezomib was required in two patients because of grade 2 neuropathy.

Conclusions:

BD is feasible and effective in LCDD patients, and it can be used as an induction regimen before ASCT.

Table n°1:

Patients characteristics

Age, sex64, M39, M50, M37, F
Immunofluorescence on renal biopsy Yes Yes Yes Yes 
Electron microscopy study on renal biopsy Yes No Yes Yes 
Prior therapy HDD HDD None HDD 
Bone Marrow plasma cells (%) 15 25 66 10 
Type of light chain involved λ 
Serum immunofixation pre/post BD Neg./Neg. k/k IgGk/IgGk IgGλ/Neg. 
Urine immunofixation pre/post BD k/k k/Neg. Neg./Neg. λ/Neg. 
sFLC (mg/L) pre/post BD 718/1060 1580/19.1 804/18 135/53.9 
sFLC R k/λ pre/post BD 27.5/36.9 83.6/0.5 152/1.1 0.57/1.09 
Serum Creatinine (mmol/L) pre/post BD 318/792 158/170 100/73 443/560 
24h Urine Protein (gr) pre/post BD 4.5/2.3 5.4/1.14 8.28/0.8 6.66/1.58 
Serum Albumin (gr/L) pre/post BD 34/36 31/35 31/40 36/40 
Serum MC& (g/L) pre/post BD 1.08/<0.6 35.7/10 1.04/Neg. 
Hematologic response to BD (Gertz MA et al., Amyloid 2010) PD VGPR PR CR 
Months without progression* NR# 10 
ASCT No Yes Yes Yes 
Hematologic response to ASCT (Gertz MA et al., Amyloid 2010) — VGPR PR CR 
Conditioning regimen = Melphalan (mg/m2— 200 200/140 140 
Age, sex64, M39, M50, M37, F
Immunofluorescence on renal biopsy Yes Yes Yes Yes 
Electron microscopy study on renal biopsy Yes No Yes Yes 
Prior therapy HDD HDD None HDD 
Bone Marrow plasma cells (%) 15 25 66 10 
Type of light chain involved λ 
Serum immunofixation pre/post BD Neg./Neg. k/k IgGk/IgGk IgGλ/Neg. 
Urine immunofixation pre/post BD k/k k/Neg. Neg./Neg. λ/Neg. 
sFLC (mg/L) pre/post BD 718/1060 1580/19.1 804/18 135/53.9 
sFLC R k/λ pre/post BD 27.5/36.9 83.6/0.5 152/1.1 0.57/1.09 
Serum Creatinine (mmol/L) pre/post BD 318/792 158/170 100/73 443/560 
24h Urine Protein (gr) pre/post BD 4.5/2.3 5.4/1.14 8.28/0.8 6.66/1.58 
Serum Albumin (gr/L) pre/post BD 34/36 31/35 31/40 36/40 
Serum MC& (g/L) pre/post BD 1.08/<0.6 35.7/10 1.04/Neg. 
Hematologic response to BD (Gertz MA et al., Amyloid 2010) PD VGPR PR CR 
Months without progression* NR# 10 
ASCT No Yes Yes Yes 
Hematologic response to ASCT (Gertz MA et al., Amyloid 2010) — VGPR PR CR 
Conditioning regimen = Melphalan (mg/m2— 200 200/140 140 
#

NR: non responder.

*

from the end of BD cycles to HDM and ASCT.

&

MC= Monoclonal Component.

Disclosures:

Off Label Use: Bortezomib for light chain deposition disease.

Author notes

*

Asterisk with author names denotes non-ASH members.