Download Treatment

Multiple Myeloma:
Is it now a curable disease?
Pritesh Patel, MD
OVERVIEW
• Disease overview
• How I approach initial treatment
• Treatment considerations at relapse
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
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
MYELOMA CELLS
Impaired immune
system
M Protein
Grow in bone marrow
Bone related signs
and symptoms
Anemia
10-35%
Lytic
Lesions
70%
Bone High blood
Pain
calcium
50%
15-20%
Infection
15%
Kidney
failure
25-30%
Neuropathy
5%
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
WHAT IS THE “M PROTEIN”?
Heavy
chain
Light
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
THE NATURAL HISTORY OF MYELOMA
Smoldering
Myeloma
MGUS
Late
Myeloma
Early
Myeloma
Plasma Cell
Leukemia
M-PROTEIN
100
Asymptomatic
Symptomatic
Active myeloma
1ST RELAPSE
50
20
2ND RELAPSE
1st line
PLATEAU
REMISSION
TIME
“Operational” cure
QUESTIONS AT DIAGNOSIS
1) Do I have SYMPTOMATIC myeloma?
2) What is my prognosis/ stage etc?
3) Am I eligible for stem cell transplant?
4) What initial treatment?
BONE MARROW PLASMA CELLS >10% OR BIOPSY
PROVEN PLASMACYTOMA AND ONE OF THE
FOLLOWING
Hypercalcemia: >11mg/dL or 1mg/dL higher than
Sixty
ULN percent or greater plasma cells in bone marrow
Renal impairment: >2mg/dL or clearance <40ml/min
Light chain ration of >100
Anemia: >2g/dL below LLN or < 10g/dL
MRI lesion >5mm
Bone lesions: >1 bone lesion on CT, PET or x ray,
osteopenia
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
5 YEAR SURVIVAL
60
50
40
30
20
10
0
National Cancer Institute Survival Epidemiology and End Results
Program SEER Cancer Statistics Review 1975-2012. Available at
seer.cancer.gov accessed 4/30/16
HOW IS MYELOMA STAGED?
STAGE
CRITERIA
I
β2 microglobulin
<3.5mg/dL
Albumin >3.5g/dL
AND
Normal LDH
AND standard
risk karyotype
II
Neither stage I
or II
III
β2 microglobulin
>5.5mg/dL
AND EIITHER
high LDH
OR
high risk
karyotype
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
THE PRINCIPLE OF AUTOLOGOUS TRANSPLANT
Cell freezing and
storage
Blood stem cell
mobilization
High dose
melphalan
Stem cell reinfusion
Blood counts
decrease then
and recover
RISKS AND BENEFITS OF TRANSPLANT
Benefits
Prolonging remission
“Cure” in some patients
Risks
Prolonged hospitalization
Diarrhea and mucositis
Infection
INITIAL TREATMENT- TRANSPLANT
ELIGIBLE
Induction
3-6 cycles
Auto
Transplant
Consolidation
and
maintenance
INITIAL TREATMENT- TRANSPLANT
INELIGIBLE
Induction
Maintenance
CONSIDERATIONS IN INITIAL
TREATMENT
2 vs. 3 Drugs
Kidney function
Convenience and Cost
COMMONLY USED MEDICATIONS
• Blood sugar
• Weight gain
• Sleep
distubance
Steroids
e.g. dexamethasone
• Blood
counts
• DVT risk
• Peripheral
neuropathy
Immunomodulatory
drugs
e.g. lenalidomide
Proteasome
inhibitors
e.g. bortezomib
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
IFM 2009 PHASE III RANDOMIZED TRIAL
N=700
Untreated
Patients
• Treatment: 8 cycles of
lenalidomide,
bortezomib, and
dexamethasone (RVD)
• Maintenance
lenalidomide for 1 year
• ASCT at relapse
VS.
• Treatment: RVD x 3
cycles and ASCT
• Consolidation: 2 cycles
of RVD
• Maintenance:
Lenalidomide for 1 year
Conventional
Arm
ASCT arm
• 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.
SUPPORTIVE CARE
• Anti-infection prophylaxis
– e.g. acyclovir with bortezomib
• Anti-thrombotic prophylaxis
– Risk factors include medications and
immobility
• Bone health
– Bisphosphonates and calcium
CONSIDERATIONS IN
RELAPSED MYELOMA
• When to treat?
• Which treatment to use?
– Organ dysfunction
– Side effects
– Re-treatment
NEWLY APPROVED AGENTS
FOR RELAPSED DISEASE
New generation IMIDs
Pomalidomide
New generation
proteasome inhibitors
Carfilzomib
Ixazomib
Histone Deacetylase
Inhibitors
Panobinostat
Monoclonal
antibodies
Daratumumab
Elotuzumab
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