An Overview of Multiple Myeloma

1. Dr. Alan Teh , 2012

2. Sarah Newbury, the first reported patient with multiple
myeloma.
A) Bone destruction in the sternum. (B) The patient with fractured
femurs and right humerus. (C) Bone destruction involving the femur.

3. Timeline depicting the history and treatment of multiple myeloma from 1844 to the present.
Kyle R A , Rajkumar S V Blood 2008;111:2962-2972

4.  Myeloma is a blood cancer
 Incidence : 0.7M/0.5 F per 100,000
population (NCR, 2003)
 Median age: 60 years
 1/10 as common as leukaemias

6.  Is not known for sure
 Decline in the immune system
 Biological factors
 Certain occupations
 Exposure to certain chemicals
 Exposure to radiation
 Virus

7. 7
 Cancer of plasma cells.
 Plasma cells come from B lymphocytes, and produce
antibodies (immunoglobulins).
 Myeloma cells produce abnormal immunoglobulins.
– Overproduce monoclonal protein or paraprotein.
– Ineffective immunoglobulins.
– Leads to decreased bone marrow function.
– Destruction of bone tissue.

11.  Plasma cell proliferation - > anemia, bone marrow
suppression, infection risk
 Osteoclasts - > boney lesions, fractures, increased
blood calcium
 Paraprotein, hypercalcemia -> renal failure
 Hypercalcemia – polyuria, thirst, drowsiness, coma

13.  Anemia - 73 percent
 Bone pain - 58 percent
 Elevated creatinine - 48 percent
 Fatigue/generalized weakness - 32 percent
 Hypercalcemia- 28 percent
 Weight loss - 24 percent, one-half of whom had lost ≥
9 kg
 Early stage - asymptomatic

14. 14
 Skull
 Spine
 Thoracic
 Lumbar
 Vertebrae
 Pelvis
 Long bones
 Spinal cord –
compression can occur
http://www.emedicine.com/Radio/topic460.htm#section~Introduction

15.  MGUS
Monoclonal Gammopathy of Unknown Significance
 Asymptomatic myeloma
 Symptomatic myeloma

16. Risk group
Relative
Risk
Risk @ 20
yrs
Lowest risk:
1. M protein < 1.5 g/dL
2. IgG subtype
3. Normal FLC ratio
1 5%
Any 1 factor abnormal 5.4 21%
Any 2 factors abnormal 10.1 37%
All 3 factors abnormal 20.8 58%
Rajkumar, V et al. Blood . 2005

17. When I told a friend that I have cancer, he replied
"I thought you were an Aries?".

18.  hyperCalcaemia
 Renal insufficiency
 Anaemia
 Bone lesions

21.  Paraprotein (M-protein)
serum protein electrophoresis
24 hr urine protein electrophoresis
serum Free light chain
 Bone marrow biopsy
plasma cells
chromosome analysis: Karyotyping, FISH
 Imaging
X Rays, MRI, PET scan

25. Cytogenetics

26. FISH

27. Normal Skull Xray

30. International staging system (ISS)
 Stage I — B2M <3.5 mg/L and serum
albumin ≥3.5 g/dL
 Stage II — neither stage I nor stage III
 Stage III — B2M ≥5.5 mg/L
Median overall survival for patients with ISS
stages I, II, and III are 62, 44, and 29
months

31.  High risk (median survival 25 months):
 Intermediate risk (median survival 42 months)
 Standard risk (median survival 50 months)

32. What's the difference between
God and a doctor
God doesn't think he’s a
doctor

33. Cancer cures smoking,
eventually

34. 34
• Currently incurable in most patients.
• Long-term complete responses are rare.
• Median survival with standard therapy about 3
years.
• Autologous stem cell transplant may prolong
progression free survival, but it’s not curative.
• Treatment of relapse:
– No standard therapy.
– Existing options inadequate.
New treatment options needed.

35. 35
 Conventional chemotherapy:
 Melphalan
 Doxorubicin
 Cyclophosphamide
• Radiation therapy
• Stem cell transplantation:
– Autologous
– Allogenic
• Novel therapeutics:
– Thalidomide
– Lenalidomide
– Bortezomib
Thalomid® Prescribing Information, Revlimid® Prescribing Information; Velcade® Prescribing Information
• Steroid therapy:
– Dexamethasone
– Prednisone

37.  Indications for treatment
 Risk stratification
- age
- co-morbidities
 Eligibility for stem cell transplantation

38.  Deferral of chemotherapy until progression to
symptomatic disease
 Follow these patients closely, every 3 to 4 months, with
serum protein electrophoresis, complete blood count,
serum creatinine, and serum calcium
 Metastatic bone survey should be considered annually
because asymptomatic bone lesions may develop

39.  Anemia (hemoglobin <10 g/dL or 2 g/dL below
normal)
 Hypercalcemia (serum calcium >11.5 mg/dL)
 Renal insufficiency (serum creatinine>2 mg/dL)
 Lytic bone lesions or severe osteopenia
 Extramedullary plasmacytoma

40.  Conventional chemotherapy
 Survival ≤ 3 yrs
 Transplantation
 Prolongs survival 4-5 yrs
 Novel agents targeting stromal interactions and
associated signaling pathways have superiority over
conventional chemotherapy
- increased % total responders
- increased depth of response

41.  Era of Novel therapy as frontline > Conventional
chemotherapy
 Autologous transplantation (high dose chemotherapy
and stem cell rescue) still an option for younger
patients

42.  Examples of current Novel agent combinations:
 Thalidomide based : TD, CTD, MPT
 Bortezomib (Velcade) based:
Vdex, VMP, CVD, PAD, VRD
 Lenalidomide (Revlimid) based: LenDex, Lendex

43.  Younger patients
 Timing
 Upfront after initial therapy with novel
agents
 Salvage for relapse
 Single vs Tandem (Double)
 Low TRM - <3%

44.  Age >70 years
 Significant comorbities (organ function)
 Poor performance status

45.  Generally not recommended (outside of
clinical trials)
 High incidence of GVHD
 High TRM (> 40%)

46.  Radiotherapy
 Surgery
 Bone care – bisphosphonates
 Transfusions
 Growth factors
 Treatment and prevention of infections
 Monitoring, management and prevention of
s/e

49.  Unexpected new long-term complications
 Second cancers
 Long-term maintenance for survivors:
quality of life
 Family/social problems
 Financial/insurance concerns
 Other

50. 50
 MM patients are expected to live longer
 Proper health maintenance contributes toward
longer survival and quality of life

51.  Biochemical
- significant increase in M-protein
 Clinical
- CRAB criteria
 Importance of monitoring and follow-up

54. New drugs on the horizon
 Carfilzomib
 Pomalidomide
 Panobinostat
 Vorinostat
 Elotuzumab
Old drugs with new use
 Bendamustine

55.  Be informed
 http://myeloma.org
 Group support
meetings
support groups
 http://malaysianmedicine.com
– Myeloma Support Group

56. Myeloma Info mobile application
mobile browser:
http://malaysianmedicine.com/myelomainfo