Light chain deposition disease (LCDD) and renal light chain (AL) - - PowerPoint PPT Presentation

Light chain deposition disease (LCDD) and renal light chain (AL) amyloidosis: different clinical presentation and renal outcome.

Paolo Milani1, Tamara Berno2, Holly Lee3, Marco Basset1, Marcello Riva2, Mario Nuvolone1, Victor Jimenez-Zepeda3, Andrea Foli1, Giampaolo Merlini1, Giovanni Palladini1

• 1. Amyloidosis Research and Treatment Center, Department of Molecular Medicine, Foundation IRCCS

Policlinico San Matteo and University of Pavia, Pavia, Italy

• 2. University of Padova, Italy
• 3. University of Calgary, Canada

Disclosure of Conflict of Interest

Nature of relationship(s)

Name of for-profit or not-for-profit

• rganization(s)

Description of relationship(s) Any direct financial payments including receipt of honoraria

Janssen, Pfizer Honoraria

Membership on advisory boards or speakers’ bureaus Funded grants or clinical trials Patents on a drug, product or device All other investments or relationships that could be seen by a reasonable, well- informed participant as having the potential to influence the content of the educational activity

❑ I have a relationship with a for-profit and/or a not-for-profit organization to disclose

Publications with LCDD patients: Pozzi et al. AJKD 2003 Sayed et al. Blood 2015 Kourelis et al. AJH 2016 Mohan et al. AJH 2016

Bridoux et al, Kidney Internat 2015

Introduction

Light chain deposition disease, LCDD

82% 66% 17% 14% 12% 9%

Stage I: both proteinuria 5g/24h and eGFR 50 mL/min per 1.73 m2 Stage II: either proteinuria >5g/24h or eGFR <50 mL/min per 1.73 m2 Stage III: both proteinuria >5g/24h and eGFR <50 mL/min per 1.73 m2 Palladini et al. Blood 2014

Data from 1065 patients with AL amyloidosis from the Pavia database

Introduction

Light chain (AL) amyloidosis

• We compare two consecutive series of LCDD and renal AL amyloidosis.
• Renal survival was defined as the time from diagnosis to dialysis initiation.

74 patients with LCDD:

• 61 from the Pavia Amyloid Center
• 8 from the Padova Hospital
• 5 from the Calgary Hospital

All patients had a biopsy proven diagnosis

• f LCDD and are treated and followed at the

referral center. 207 patients with AL amyloidosis from the Pavia Amyloidosis Center All patients had a biopsy proven diagnosis

• f AL amyloidosis

Only patients with Mayo2004 cardiac stage I (NT-proBNP <332 ng/L & cTnI< 0.1 ng/mL) were included in the study.

Methods

Variables LCDD (N=74) AL amyloidosis (N=207) P Age at diagnosis, median 56 (46-61) 62 (54-69) <0.001 Sex, male 43 (58) 112 (54) 0.278 eGFR, median 32 (19-51) 70 (49-88) <0.001 CKD stage 1 (eGFR>90) 5 (7) 46 (22) <0.001 CKD stage 2 (eGFR: 60-89) 6 (8) 83 (40) <0.001 CKD stage 3 (eGFR: 30-59) 24 (32) 51 (25) 0.126 CKD stage 4 (eGFR 15-29) 23 (31) 20 (9) <0.001 CKD stage 5 (eGFR <15) 8 (11) 8 (3) 0.028 Dialysis at diagnosis 8 (11) 2 (1) <0.001 Proteinuria, median 2.6 (0.7-5.7) 6.2 (3.5-9.9) <0.001 Nephrotic range proteinuria 29 (39) 159 (77) <0.001

5 10 15 20 25 Proteinuria, g/24h LCDD (N=74) Proteinuria, g/24h AL (N=207) 20 40 60 80 100 120 140 160 eGFR, mL/min LCDD (N=74) eGFR, mL/min AL (N=207)

Results: patients characteristics’

eGFR, P<0.001 Proteinuria, P<0.001

Results: patients characteristics’

Variables LCDD (N=74) AL amyloidosis (N=207) P Kappa:lambda LC type 63 (85): 11 (15) 48 (23) : 157 (76) <0.001 dFLC, mg/L 190 (44-668) 75 (25-263) <0.001 iFLC, mg/L 257 (72-703) 91 (44-290) <0.001 BMPC %, median 10 (6-15) 10 (6-14) 0.210

10 20 30 40 50 60 BMPC, % LCDD (N=74) BMPC, % AL (N=207)

BMPC, P=0.210

• 500

500 1000 1500 2000 2500 3000 3500 4000 dFLC, mg/L LCDD (N=74) dFLC, mg/L AL (N=207)

dFLC, P<0.001

20 40 60 80 100 24 48 72 96 120 144 168 Time (months)

AL amyloidosis, median not reached LCDD, median 9 years P<0.001 42/207 (19%) patients with AL required dialysis. 10 patients received renal transplant 32/74 (43%) patients with LCDD required dialysis. 5 patients received renal transplant

Results: renal survival

Significant predictors of renal outcome at univariate analysis

Variable HR (95% CI) P eGFR 0.95 (0.93-0.98) 0.001 Proteinuria 1.03 (0.94-1.13) 0.418 eGFR >30 mL/min eGFR <30 mL/min Variable HR (95% CI) P eGFR 0.95 (0.93-0.96) <0.001 Proteinuria 1.10 (1.04-1.16) <0.001

Stage I: both proteinuria 5g/24h and eGFR 50 mL/min per 1.73 m2 Stage II: either proteinuria >5g/24h or eGFR <50 mL/min per 1.73 m2 Stage III: both proteinuria >5g/24h and eGFR <50 mL/min per 1.73 m2

Light chain deposition disease, LCDD Light chain (AL) amyloidosis

P<0.001 P=0.001 P<0.001

Type of therapy, 1° line N (%) Bortezomib 34 (46) Oral melphalan 19 (27) High dose DEX 12 (16) Thalidomide 4 (5) Bendamustine/rituximab 1 (1) ASCT, yes 1 (1) Other 3 (4) Autologous stem cell transplant, ASCT: 4 patients Median n. of lines of therapy: 2 (range: 2-5) Second or subsequent therapies: Lenalidomide, Pomalidomide, Daratumumab. Less than VGPR, median 5 years P <0.001 Response to 1° line N (%) Overall Hem Response 25 (34) CR / VGPR / PR 18 (24) / 3 (4) / 4 (6)

Results: response to therapy in LCDD

CR/VGPR

Conclusions

• The clinical presentation and outcome of LCDD and renal AL amyloidosis

are different;

• LCDD is characterized by a more advanced renal dysfunction, less

pronounced proteinuria and faster progression to dialysis;

• Achievement of CR/VGPR after first line therapy according to ISA criteria

is associated with a significant decrease in progression to dialysis (0 vs. 45% in 4 years).

Acknowledgements

Pavia Amyloidosis Research and Treatment Center: Marco Basset, Mario Nuvolone, Francesca Lavatelli, Roberta Mussinelli, Stefano Perlini, Andrea Foli, Giampaolo Merlini, Giovanni Palladini Padova University Hospital: Tamara Berno, Marcello Riva. Calgary university Hospital: Holly Lee, Victor Jimenez-Zepeda