1. The Importance of Survivorship in Multiple Myeloma

2. Multiple Myeloma is… A cancer of bone marrow plasma cells Incurable but very treatable A cancer in which the side effects of treatment are manageable Exciting as newer agents offer hope of improved survival SEER data—5-year OS 26%  33% over last decade Faiman, B. (2010). Treatment modalities: Newly Diagnosed, Non-transplant Eligible.

3. Immunoglobulin Structure and Dysfunction Immunoglobulins: Integral to immune system function Dysfunction of Heavy and light chains Heavy: IgG, IgA, IgD and IgE Light: Kappa, Lambda Serum Kappa/Lambda Free Light Chains Non-secretory MM

4. Diagnostic Tests Blood and Urine Tests –Generic blood analysis Complete blood cell counts (CBC) Calcium, uric acid and creatinine Albumin, Beta-2-microglobulin, LDH –M proteins Blood—Serum protein electrophoresis and Immunofixation Urine protein electrophoresis and immunofixation Quantitative Immunoglobulins, serum free light chain assay Radiologic Skeletal survey; MRI/computerized tomography (CT) scanning or PET if needed Bone Marrow Aspirate and biopsy with karyotyping and plasma cell labeling index

5. Criteria for Diagnosis of MM Monoclonal plasma cells in bone marrow (  10%/  30% if non-secretory) Monoclonal protein present in serum and/or urine Myeloma-related organ dysfunction –Calcium  in serum (>10.5 mg/L) –Renal insufficiency (SCr >2 mg/dL) –Anemia (hemoglobin <10 g/dL or 2g <normal) –Bone lesions or osteoporosis Durie BGM et al. Hematol J. 2003;4:379 Kyle RA et al. Mayo Clin Proc. 2003;78:21

6. Kaplan-Meier Curve for Myeloma patients 1975-2004

8. Myeloma Survivorship Calculation of Years of Life Lost by Age Adjusted Relative Survival by Age

9. What to look for… Unexpected long term complications Second cancers (alkylating agents) Maintenance vs. No maintenance Sexuality issues Family/Social problems Financial/Insurance concerns Other

10. Impact of Survival in MM with Novel Agents Wang et al (2010)

11. Thalidomide (Thalomid ® ) FDA approved for newly diagnosed and relapsed MM Patients who receive thalidomide had improved survival over patients receiving steroids in clinical trials When given to patients after transplant, thalidomide has been shown to improve survival and extend remission Celgene Package Insert; Attal et al, 2005; Rajkumar et al, 2004

12. Side Effects of Thalidomide Common –Birth defects –peripheral neuropathy –Somnolence, Fatigue –Rash –Constipation –DVT (common in combination with Dex or other agents) Less Common –Stevens-Johnson syndrome (adverse reaction to drugs) –Elevated liver enzymes –Malaise –Peripheral edema

13. Bortezomib (Velcade ® ) FDA approved for newly diagnosed and relapsed MM Has been shown to improve survival in elderly patients with newly diagnosed MM compared to dex, MP or VMP Extends remissions in patients with relapsed MM

14. Frequent Side Effects of Bortezomib Thrombocytopenia Asthenia –Fatigue, weakness GI effects –Nausea, vomiting, diarrhea Peripheral neuropathy Hypotension Velcade [package insert]. Cambridge, MA: Millennium Pharmaceuticals, Inc; 2007.

15. Lenalidomide (Revlimid ® ) FDA approved for relapsed MM Clinical trials have demonstrated improved remission rates in combination with dexamethasone and bortezomib Will extend progression free survival in elderly patients when len is given after MPR Extends remission after transplant

16. Lenalidomide Only available through restricted distribution program “RevAssist SM ” because of potential for human birth defects. Different toxicity profile than thalidomide –Greater myelosuppression –Fatigue, Asthenia –Renally excreted –GI Revlimid ® (lenalidomide) prescribing information. Available at: http://www.celgene.com/PDF/RevlimidPI.pdf

17. Bone Health: Scope of Problem Over 58% of patients have back and bone pain at diagnosis 15%-30% develop VCFs annually leads to altered biomechanics and increases risk of health problems About half of patients with at least 1 osteolytic lesion develop pathologic fractures within 9 months Patients at risk for pain, hypercalcemia, decreased mobility and spontaneous fractures if MM not controlled 1.McClosekey et al. Br J Hematol. 1998;100:317-325. 2.Ray et al. J Bone Min Res. 1997;12:24-35. 3.McCloskey et al. Drugs. 2001;61:1253-1274. 4.Berenson et al. NEJM. 1996;334:488-493.

18. Pathobiology of Bone Disease Pathobiology: malignant cells produce osteoclast- activating factors that destroy bone cells –Osteoclast stimulation leads to extensive osteolysis, severe bone pain, and pathologic fractures –Spinal cord compression Skeletal survey, MRI, CT, PET to diagnose Treatment: Analgesia, bisphosphonaes, treat disease if relapse, vertebroplasty or balloon kyphoplasty

19. Kidney Dysfunction Bence-Jones proteinuria/Free monoclonal light Chains: Incidence ~70% Light chain Igs can precipitate and damage renal cells Free light chains filtered in the nephron’s glomerulus, then absorbed and metabolized by proximal tubular cells Heavy and light chains can cause renal tubular damage Serum Free light chain assay more reliable than urine –ATN secondary to NSAID use, dehydration, nephrotoxic agents (CT dyes) –Supportive therapy Hydration, correct underlying cause with treatment Avoid IV contrast and nephrotoxic agents (IV dyes, NSAIDS, aminoglycosides especially) Plasmapheresis, dialysis

20. Conclusions Patients with MM are living longer than ever! Nurses are in a unique position to educate patients, assess for side effects, and intervene when appropriate New and unidentified survivorship issues may become apparrent