Multiple Myeloma: Is it now a curable disease?

1. Multiple Myeloma: Is it now a curable disease? Pritesh Patel, MD

2. OVErview • Disease overview • How I approach initial treatment • Treatment considerations at relapse

3. How many people are affected by myeloma? ≈96,000 MM patients National Cancer Institute Survival Epidemiology and End Results Program SEER Cancer Statistics Review 1975-2012. Available at seer.cancer.gov accessed 4/30/16

4. How many people are affected by myeloma? ≈30,000 new diagnoses National Cancer Institute Survival Epidemiology and End Results Program SEER Cancer Statistics Review 1975-2012. Available at seer.cancer.gov accessed 4/30/16

5. Myeloma cells M Protein Impaired immune system Grow in bone marrow Bone related signs and symptoms Anemia 10-35% Kidney failure 25-30% Bone Pain 50% Neuropathy 5% Lytic Lesions 70% High blood calcium 15-20% Infection 15%

7. What is the “m Protein”? Heavy chain Protein normally made by plasma cells Single type produced by myeloma cells Can be measured at diagnosis in urine and blood Level can be tracked for disease response and relapse Light chain

8. The natural history of myeloma Late Myeloma Plasma Cell Leukemia M-PROTEIN 100 Symptomatic Asymptomatic 2ND RELAPSE Activemyeloma 50 1ST RELAPSE 20 1st line PLATEAU REMISSION TIME “Operational” cure

9. Questions at diagnosis • Do I have SYMPTOMATIC myeloma? • What is my prognosis/ stage etc? • Am I eligible for stem cell transplant? • What initial treatment?

10. bone marrow plasma cells >10% or biopsy proven plasmacytoma and one of the following C Hypercalcemia: >11mg/dL or 1mg/dL higher than ULN S Sixty percent or greater plasma cells in bone marrow R Renal impairment: >2mg/dL or clearance <40ml/min Li Light chain ration of >100 A Anemia: >2g/dL below LLN or < 10g/dL M MRI lesion >5mm B Bone lesions: >1 bone lesion on CT, PET or x ray, osteopenia

11. Baseline testing

12. 5 year survival National Cancer Institute Survival Epidemiology and End Results Program SEER Cancer Statistics Review 1975-2012. Available at seer.cancer.gov accessed 4/30/16

13. How is myeloma staged? STAGE I II III β2 microglobulin <3.5mg/dL Albumin >3.5g/dL AND Normal LDH AND standard risk karyotype β2 microglobulin >5.5mg/dL AND EIITHER high LDH OR high risk karyotype Neither stage I or II CRITERIA

14. Who can undergo stem cell transplant? • Decision based largely on functional class and comorbid illness • Can be performed safely in many patients in 70s • Patient choice

15. The principle of autologous transplant Cell freezing and storage Blood counts decrease then and recover Stem cell re-infusion High dose melphalan Blood stem cell mobilization

16. Risks and benefits of transplant

17. Initial treatment- transplant eligible

18. Initial treatment- transplant ineligible

19. Considerations in initial treatment

20. Commonly used medications

21. Principle of “maintenance” • Initial therapy reduces disease • Maintenance is a less intensive phase of therapy • Maintain remission as long as possible without significant compromise of quality of life

22. IFM 2009 Phase III Randomized Trial N=700 Untreated Patients VS. • Results (f/u 39 months) • Complete remission 58% in ASCT arm vs. 46% in RVD arm • 3-year PFS 61% in ASCT arm vs. 48% in RVD arm • Median OS similar at 3 years (88%) Attal, et al. Blood. 2015; 126: abst 391.

23. Supportive care • Anti-infection prophylaxis • e.g. acyclovir with bortezomib • Anti-thrombotic prophylaxis • Risk factors include medications and immobility • Bone health • Bisphosphonates and calcium

24. Considerations in Relapsed myeloma • When to treat? • Which treatment to use? • Organ dysfunction • Side effects • Re-treatment

25. Newly Approved agents for relapsed disease

26. Summary • Prolonged remissions are achievable in 2016 • Goal to achieve deep response • Maintained with less intense therapy • Now a large number of options at relapse