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
Rare disease
Second most common hematologic malignancy
National Cancer Institute Survival Epidemiology and End Results Program SEER Cancer Statistics Review Available at seer.cancer.gov accessed 4/30/16

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

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

6. Production and release of clonal immunoglobulin into blood and/or urine
Destruction and invasion of bone marrow cavity
Impaired immune function
High blood calcium and bone complications

7. What is the “m Protein”? Protein normally made by plasma cells
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
MGUS
Smoldering Myeloma
Early Myeloma
Late Myeloma
Plasma Cell Leukemia
M-PROTEIN
100
Asymptomatic
Symptomatic
Active myeloma
2ND RELAPSE 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
Hypercalcemia: >11mg/dL or 1mg/dL higher than ULN
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 Complete blood count Complete chemistry
B2 microglobulin and albumin
Electrophoresis, immunofixation, free light chains
Bone marrow aspirate and biopsy
FISH testing
Cytogenetics
Skeletal survey
Consideration of MRI and PET/CT

12. 5 year survival
National Cancer Institute Survival Epidemiology and End Results Program SEER Cancer Statistics Review 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
Stem cell re-infusion
Blood counts decrease then and recover
High dose melphalan
Blood stem cell mobilization

16. Risks and benefits of transplant
Prolonging remission
“Cure” in some patients
Risks
Prolonged hospitalization
Diarrhea and mucositis
Infection

17. Initial treatment- transplant eligible
Induction
3-6 cycles
Auto Transplant
Consolidation and maintenance

18. Initial treatment- transplant ineligible
Induction
Maintenance

19. Considerations in initial treatment
2 vs. 3 Drugs
Kidney function
Convenience and Cost

20. Commonly used medications
Blood sugar
Weight gain
Sleep distubance
Steroids
e.g. dexamethasone
Blood counts
DVT risk
Immunomodulatory drugs
e.g. lenalidomide
Peripheral neuropathy
Proteasome inhibitors
e.g. bortezomib

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
Treatment: 8 cycles of lenalidomide, bortezomib, and dexamethasone (RVD)
Maintenance lenalidomide for 1 year
ASCT at relapse
Conventional Arm
Treatment: RVD x 3 cycles and ASCT
Consolidation: 2 cycles of RVD
Maintenance: Lenalidomide for 1 year
ASCT arm
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 Anti-thrombotic 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
New generation IMIDs
Pomalidomide
New generation proteasome inhibitors
Carfilzomib
Ixazomib
Histone Deacetylase
Inhibitors
Panobinostat
Monoclonal antibodies
Daratumumab
Elotuzumab

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