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 M Protein

system

Grow in bone marrow

Bone related signs

and symptoms

Anemia Lytic Bone High blood Infection Kidney Neuropathy

10-35% Lesions Pain calcium 15% failure 5%
70% 50% 15-20% 25-30%
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 Protein normally made by plasma
cells
Light
Single type produced by myeloma
chain
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 Early Late Plasma Cell

MGUS
Myeloma Myeloma Myeloma Leukemia

M-PROTEIN

100
Asymptomatic Symptomatic
Active myeloma 2ND RELAPSE

50 1ST RELAPSE

20
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

C
S
Hypercalcemia: >11mg/dL or 1mg/dL higher than
Sixty
ULN 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
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

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 I II III

β2 microglobulin β2 microglobulin
<3.5mg/dL Neither stage I >5.5mg/dL
Albumin >3.5g/dL or II AND EIITHER
CRITERIA
AND high LDH
Normal LDH OR
AND standard high risk
risk karyotype 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

Stem cell re- Blood counts

High dose infusion decrease then
melphalan and recover
Blood stem cell
mobilization
RISKS AND BENEFITS OF TRANSPLANT

Benefits
Prolonging remission
“Cure” in some patients

Risks
Prolonged hospitalization
Diarrhea and mucositis
Infection
INITIAL TREATMENT- TRANSPLANT
ELIGIBLE

Induction Consolidatio
Auto
n and
3-6 cycles Transplant
maintenance
INITIAL TREATMENT- TRANSPLANT
INELIGIBLE

Maintenanc
Induction
e
CONSIDERATIONS IN INITIAL
TREATMENT

2 vs. 3 Drugs

Kidney function

Convenience and Cost

 COMMONLY USED MEDICATIONS

• Blood sugar • Blood counts • Peripheral

• Weight gain • DVT risk neuropathy
• Sleep
distubance
Immunomodulatory Proteasome
Steroids
drugs inhibitors
e.g. dexamethasone
e.g. lenalidomide 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

• Treatment: 8 cycles of • Treatment: RVD x 3

lenalidomide, cycles and ASCT
bortezomib, and • Consolidation: 2 cycles
dexamethasone (RVD) of RVD
N=700 • Maintenance • Maintenance:
VS.
Untreated lenalidomide for 1 year Lenalidomide for 1 year
Patients • ASCT at relapse

Conventional
ASCT arm
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
New generation IMIDs proteasome inhibitors
Pomalidomide Carfilzomib
Ixazomib

Monoclonal
Histone Deacetylase
antibodies
Inhibitors
Daratumumab
Panobinostat
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