Early Reduction of Serum-Free Light Chains Associates with Renal Recovery in Myeloma Kidney

1. Early Reduction of Serum-Free Light Chains Associates with Renal Recovery in Myeloma Kidney Sophina Hissaund FY2

2. Aims • Myeloma • The Study • Treatment • Results • Survival • Conclusion • Discussion

3. Myeloma • Malignant clonal proliferation of B-lymphocyte derived plasma cells • A single clone of plasma cells produce identical immunoglobulins seen as a monoclonal band, or paraprotein, on serum or urine electrophoresis

4. Myeloma Kidney • Myeloma kidney can cause severe irreversible renal failure in patients with multiple myeloma • The tubulointerstitial injury is a consequence of high concentrations of circulating monoclonal FLCs produced by a clonal expansion of plasma cells

5. The Study • To determine the relationship between the achieved early FLC reduction and renal recovery • University Hospital Birmingham and Mayo Clinic, Rochester, Minnesota • 39 patients • 23 male, 16 female • Median age 62 years

6. The Study • Severe renal failure at presentation • Biopsy proven myeloma kidney • 79% first presentation of myeloma • 15% MGUS before diagnosis • 24 patients required dialysis support

8. Treatment • Birmingham • combination of extended haemodialysis with thalidomide-based chemotherapy for patients with new presentation of myeloma • Bortezomib for relapsing disease

9. Treatment • Minnesota • Plasma exchange in combination with chemotherapy regimen consisting of high dose steroids used alone or with Bortezomib, thalidomide, melphalan, vincristine, doxorubicin or alemtuzumab

11. Results Day 12 – each increment of 10% FLC reduction was associated with a 60% increase in likelihood of renal recovery

12. Results Day 21 –an additional 10% FLC reduction was associated with 60% increased likelihood of recovery

14. The relationship of reduction in serum FLCs and renal recovery is linear in patients with myeloma kidney Results

15. Long Term Survival Outcomes • Median survival of patients who recovered renal function was 42.7 months • Risk of death 3x lower for patients with a new myeloma and those with renal recovery • Patients with λ FLCs had a significant higher likelihood of death

16. Long Term Survival Outcomes No significant association between % reduction of serum FLC concentration and survival

17. Conclusion • No absolute threshold by which FLCs must be reduced to facilitate renal recovery • To enable a renal recovery rate of 80%, a 60% reduction in FLC levels by day 21 is required • Targeting treatment to reverse renal failure in myeloma kidney by early reduction of FLCs is critical

18. Discussion • Combination • Plasma exchange • Biopsy results • Pre –existing renal disease • Small study

19. Thank you