1. Interaction between MM cells and bone marrow environment critical for tumor growth and propagation osteoclast Myeloma cells Normal bone

2. Intravenous bisphosphonates (zoledronic acid, pamidronate) appear to be superior to oral agents (Fosamex); Zometa conferred survival benefit over placebo

3. Same pt after rx, transplant, Bisphosphonates, 18 mo later

4. Bisphosphonates recommended for all patients with lytic bone disease, monthly for 24 months Restart at time of relapse After two years of continuous, unclear what should be recommended--? Every 3- 6 months

5. what’s abnormal here is the amount of exposed bone Osteonecrosis of the jaw (ONJ)-

6. Copyright ©2006 American Society of Hematology. Copyright restrictions may apply. Hematology 2006;2006:505-516 Figure 1. Duration of exposure prior to clinical presentation Zometa appears more likely than other bisphosphonates to cause osteonecrosis but all of the agents can; unclear if dental screening is warranted prior to starting bisphosphonates

7. Other drugs that might help bone? Denosumab (Xgeva) vs Zometa trial- ongoing in newly diagnosed myeloma patients Results out in two years Some data suggests that bortezomib (velcade) and carfilzomib (kyprolis) may also help build bone while treating myeloma

8. Pain Management

9. Back pain statistics (why did they miss my myeloma?) 2.4 % of all ER visits (2.4 million annually) for this symptom Three months after ER visit, 46% of pts still using pain meds, 42% still had mild to severe pain-so repeat visits don’t necessarily clue in medical staff Myeloma back pain-worsens with time, worse with activity, worse as day goes on Myeloma patients-goal is to prevent serious complications-spinal cord compression that could cause paralysis, fractures-severe pain, loss of movement needs immediate intervention

10. Immediate Interventions for newly diagnosed pts Complete evaluation to understand pain source-x-rays, MRI often very helpful, consultants-orthopedics, neurosurgery Sometimes surgery is necessary Braces-uncomfortable but can help Radiation therapy Steroids to reduce inflammation

11. PAIN MEDICATIONS STEP 1: acetaminophen, ibuprofen, naproxen, piroxicam, meloxicam, celecoxib, aspirin STEP 2: “weak” opioid- hydrocodone with acetaminophen (norco, vicodin, lortab); acetaminophen with oxycodone (percocet) STEP 3: stronger opiods-morphine, oxycodone, fentanyl, oxymorphone, methadone

12. WHO Model has been criticized: Some useful drugs do not fit into this model well: tramadol flexeril gabapentin, pregabalin Many myeloma patients benefit from drug class combinations: E.g. long acting morphine + Tylenol+ nortriptyline+gabapentin

13. Formal tools to assess pain: Brief Pain Inventory

14. visual analog scale Reduction or increase in two points is considered significant; IF YOU ARE OFFERED THE CHANCE TO USE THESE SCALES, DO SO!

15. What’s the best treatment for pain?

16. OPIATE PAIN MEDICATIONS LONG ACTING: dosed 1-3x daily MS contin Oxycontin Methadone Fentanyl patch SHORT ACTING: (last 2-6 hours) Morphine IR Oxycodone Hydrocodone/APAP (Vicodin) Hydromorphone (dilaudid) Fentanyl lozenges Oxycodone/APAP (percocet)

17. STARTING POINT: combination of long and short acting medications Addition of gabapentin, tricyclic (nortriptyline, etc.) If you are taking more than 4 extra doses of short acting, need to consider increasing long acting If you are too sleepy, long acting should be reduced Very severe pain-pain pumps (PCA), implantable pumps, home IV therapy (home bound), single radiation treatment

18. Most patients get acclimated to nausea Opiates always cause constipation Tapering advised when cutting Excessive Tylenol may not be healthy for liver Patients with very low platelet counts, kidney problems should use aspirin and ibuprofen cautiously BUT THESE DRUGS SHOULD BE CONSIDERED

19. Peripheral neuropathy

20. Interaction between MM cells and bone marrow environment critical for tumor growth and propagation osteoclast Myeloma cells Normal bone

21. Intravenous bisphosphonates (zoledronic acid, pamidronate) appear to be superior to oral agents (Fosamex); Zometa conferred survival benefit over placebo

22. Same pt after rx, transplant, Bisphosphonates, 18 mo later

23. Bisphosphonates recommended for all patients with lytic bone disease, monthly for 24 months Restart at time of relapse After two years of continuous, unclear what should be recommended--? Every 3-6 months

24. what’s abnormal here is the amount of exposed bone Osteonecrosis of the jaw (ONJ)-

25. Copyright ©2006 American Society of Hematology. Copyright restrictions may apply. Hematology 2006;2006:505-516 Figure 1. Duration of exposure prior to clinical presentation Zometa appears more likely than other bisphosphonates to cause osteonecrosis but all of the agents can; unclear if dental screening is warranted prior to starting bisphosphonates

26. Other drugs that might help bone? Denosumab (Xgeva) vs Zometa trial-ongoing in newly diagnosed myeloma patients Results out in two years Some data suggests that bortezomib (velcade) and carfilzomib (kyprolis) may also help build bone while treating myeloma

27. Pain Management

28. Back pain statistics (why did they miss my myeloma?) 2.4 % of all ER visits (2.4 million annually) for this symptom Three months after ER visit, 46% of pts still using pain meds, 42% still had mild to severe pain-so repeat visits don’t necessarily clue in medical staff Myeloma back pain-worsens with time, worse with activity, worse as day goes on Myeloma patients-goal is to prevent serious complications-spinal cord compression that could cause paralysis, fractures-severe pain, loss of movement needs immediate intervention

29. Immediate Interventions for newly diagnosed pts Complete evaluation to understand pain source-x-rays, MRI often very helpful, consultants-orthopedics, neurosurgery Sometimes surgery is necessary Braces-uncomfortable but can help Radiation therapy Steroids to reduce inflammation

30. PAIN MEDICATIONS STEP 1: acetaminophen, ibuprofen, naproxen, piroxicam, meloxicam, celecoxib, aspirin STEP 2: “weak” opioid- hydrocodone with acetaminophen (norco, vicodin, lortab); acetaminophen with oxycodone (percocet) STEP 3: stronger opiods-morphine, oxycodone, fentanyl, oxymorphone, methadone

31. WHO Model has been criticized: Some useful drugs do not fit into this model well: tramadol flexeril gabapentin, pregabalin Many myeloma patients benefit from drug class combinations: E.g. long acting morphine + Tylenol+ nortriptyline+gabapentin

32. Formal tools to assess pain: Brief Pain Inventory

33. visual analog scale Reduction or increase in two points is considered significant; IF YOU ARE OFFERED THE CHANCE TO USE THESE SCALES, DO SO!

34. What’s the best treatment for pain?

35. OPIATE PAIN MEDICATIONS LONG ACTING: dosed 1-3x daily MS contin Oxycontin Methadone Fentanyl patch SHORT ACTING: (last 2-6 hours) Morphine IR Oxycodone Hydrocodone/APAP (Vicodin) Hydromorphone (dilaudid) Fentanyl lozenges Oxycodone/APAP (percocet)

36. STARTING POINT: combination of long and short acting medications Addition of gabapentin, tricyclic (nortriptyline, etc.) If you are taking more than 4 extra doses of short acting, need to consider increasing long acting If you are too sleepy, long acting should be reduced Very severe pain-pain pumps (PCA), implantable pumps, home IV therapy (home bound), single radiation treatment

37. Most patients get acclimated to nausea Opiates always cause constipation Tapering advised when cutting Excessive Tylenol may not be healthy for liver Patients with very low platelet counts, kidney problems should use aspirin and ibuprofen cautiously BUT THESE DRUGS SHOULD BE CONSIDERED

38. Peripheral neuropathy