1. ONS Update: New Approaches to Renal Insufficiency Beth Faiman RN, MSN, APRN-BC, AOCN Nurse Practitioner, Cleveland ClinicTaussig Cancer Institute Pre-Doctoral Research Fellow, Case Western Reserve University

2. Kidney Dysfunction and Multiple Myeloma Kidney dysfunction is one of the common clinical features of symptomatic MM 20% to 60% of patients will present with some degree of insufficiency or renal failure The National Kidney Foundation (NKF) Clinical Practice Guidelines5 defined renal failure as serum creatinine levels of greater that 3.0 mg/dL Affects OS and QOL Higher risk for infections and anemia

3. Who is at risk? MM who have kappa or lambda light chain (Bence Jones protein) proteinuria renal disease in patients with MM is heterogeneous, careful attention must be paid when selecting an appropriate therapy and supportive care measures to decrease progression to ESRD and dialysis.

4. Renal Failure - Physiology Tubular capacity for reabsorption exceeded by excess light chain production Filtered light chains bind to Tamm-Horsfall glycoprotein Cast formation and obstruction in the distal nephron Heavy and light chains can cause tubular damage Serum Free light chain assay more reliable than urine

5. Renal Failure Confounding factors- ATN –Hypercalcemia/Hyperuricemia –Volume depletion, loop diuretics –Nephrotoxic agents (IV contrast, NSAIDS, aminoglycosides) –Amyloidosis, LCCD –Other comorbidities (HTN, poorly controlled DM)

6. Diagnosis Cr >2 SFLC non-secretory MM fail to secrete measurable amounts of m protein = challenge for monitoring of disease. sFLC assay relies on an imbalance between kappa and lambda light chains and is a surrogate marker for monoclonality.

7. Renal Failure- Supportive treatment Supportive therapy –Avoid IV contrast and nephrotoxic agents Hydration –Correct underlying cause ATN, hypovolemia, MM –Plasmapheresis- 3 prospective trials favor; 1 did not –Dialysis- may reverse renal failure MONITOR Urine output, character, chem and cbc

8. Treatment- Newer agents = hope Goal: no dialysis!! Steroids HDDex Bortezomib safe cr cl <13.8ml/min, reverse RF Thal safe, no dose redux Len: dose redux or lead to myelosuppression Melphalan dose redux Bisphosphonates – Pam, zometa Monitoring- cbc, chem, disease status

9. New insights to novel therapies in MM Beth Faiman RN, MSN, APRN-BC, AOCN Nurse Practitioner, Cleveland ClinicTaussig Cancer Institute Pre-Doctoral Research Fellow, Case Western Reserve University

10. New insights –Upfront and Maint Upfront – VMP vs VTP mateos et al NDMM elderly –Both induction schedules highly effective similar ORR and CR, maint improved responses both ends, overcome poor cyto BMPT with BT vs bmp no maint 2y PFS 70v58, OS no difference MP vs MPT – 1571 pts- PFS and OS MPT Maintenance MP vs MPR vs MPR-R –MPR-R reduced risk progression by 50% vs MP –fIrst trial to document Len maint

11. What do I watch out for in patients with renal failure Beth Faiman RN, MSN, APRN-BC, AOCN Nurse Practitioner, Cleveland Clinic Taussig Cancer Institute Pre-Doctoral Research Fellow, Case Western Reserve University

12. What do I watch out for in patients with renal failure? Kidney dysfunction is one of the common clinical features of symptomatic MM 20% to 60% of patients will present with some degree of insufficiency or renal failure The National Kidney Foundation (NKF) Clinical Practice Guidelines5 defined renal failure as serum creatinine levels of greater that 3.0 mg/dL Affects OS and QOL Higher risk for infections and anemia

13. Renal Failure Be aware of Confounding factors- ATN –Hypercalcemia/Hyperuricemia –Volume depletion, loop diuretics –Nephrotoxic agents (IV contrast, NSAIDS, aminoglycosides) –Amyloidosis, LCCD –Other comorbidities (HTN, poorly controlled DM) CBC, CHEM, urine output/character monitor disease Btz, Len, thal; most new agents on the horizon not tested ; safety unknown