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