4. ETIOLOGY
• UNKNOWN
• Genetic factors – deletion of 13q14,mutation of p53 and Rb gens
• Environmental factors
• Chronic inflammations
• Infections
• Radiations
5. PATHOPHYSIOLOGY
• The pathological and clinical features of myeloma are due to
1. Tissue infiltration of abnormal plasma cells
2. Production of large amount of abnormal immunoglobulins
3. Impairment of immunity
6. MYELOMA BONE DISEASE
• In myeloma bone lesions could be
1. Discrete lytic lesion
2. Widespread osteopenia
3. Multiple lytic lesions
• Higher the number of lesions – poor prognosis
• Most common sites – Spine > ribs > pelvis, skull and long bones
• In spine primarily involves body
• INCREASED OSTEOCLASTIC ACTIVITY AND DECREASED OR ABSCENT
OSTEOBLASTIC ACTIVITY IS THE MAIN PATHOLOGY
7. MYELOMA BONE DISEASE
In contrast to normal bone remodeling , the coupling between
osteoclast and osteoblast is lost in MM
INCREASED DECREASED
OSTEOCLASTIC OSTEOBLASTIC
ACTIVITY ACTIVITY
BONE RESOPTION
8. MYELOMA BONE DISEASE
The main difference of MM from other metastatic bone disease is
Decreased or absent osteoblastic activity
In MM increased osteoclastic activity is due to
1. Increased production of RANKL
2. Increased production of other cytokines which promote bone
resorption(IL1,IL6,TNF)
3. Suppression of Osteoprotegerin(OPG)
9. CLINICAL FEATURES
• Asymptomatic in 30%
• Bone pain M/C
• Intermittent initially , later becomes
constant
• Worse with activity/wt bearing , thus
worse during day time
• Generalized malaise
• Weight loss
• Anemia,Thrombocytopenia
• Renal failure
• Hypercalcemia m/c
• Deposition of BJ proteins
• amyloidosis
17. INVST…
• MRI
• Most sensitive for bone lesions
• PET Scan
• Most sensitive for extramedullary disease
CROSS SECTIONAL IMAGING(CT,PET,MRI) > SKELETAL SURVEY
18. INVT….
• Bone scan
• Less useful
• Appears as cold
• Bone marrow examination
• Hypercellular
• Sheets of plasma cells- small round blue cells with CART WHEEL shaped
nucleus and abundant cytoplasm with a perinuclear halo
• >10% plasma cells
• Immunophenotype – CD56+
• Cytogenetics
19. WHEN TO SUSPECT
• Patient of advanced age (>60) with bone pain and pathological # at unusual
sites not associated with trauma & which does not improve with treatment,
Bone pain with lytic lesions discovered on routine skeletal films
• Increase serum protein conc; or presence of M protein in blood or urine
• Unexplained anemia with no h/o blood loss/hemolysis/anemia of chronic d/s
with normal Vit B12 and folate and iron studies
• Hypercalcemia
• Renal impairment-no clear explanation including pre renal causes,primary renal
disorders or obstructive conditions.
20. DIAGNOSTIC CRITERIA – International
myeloma working group
• Clonal bone marrow plasma cells ≥ 10 % OR Biopsy proven
plasmacytoma
Plus one of the following (CRAB/MDE)
• C- Hypercalcemia, Serum Ca >11 mg/dl
• R- Renal insufficiency – serum creatinine > 2 mg/dl
• A-Anemia, Hb <10g/dl
• B-Bone lesions, one or more osteolytic lesions ≥ 5mm
OR
21. DIAGNOSTIC CRITERIA
Any one or more of the biomarkers of malignancy
• Clonal bone marrow plasma cell ≥ 60%
• Involved:uninvolved serum free light chain ratio ≥ 100
• > 1 focal lesions on MRI
26. Solitary plasmacytoma
• Single skeletal lesion
• No plasma cells in bone marrow
• No end organ damage
• Can progress to MM
27. BAD PROGNOSIS
• Age > 65
• Hb < 10 g/dl
• Albumin <3 g/dl
• Serum β2 microglobulin > 4 mg/dl
• Platelet count < 1.5L
• Involvement of more than three bones
28. TREATMENT
• MM is not curable
• The goal of the treatment is Disease control and improved quality of
life
31. TARGATED THERAPY
Targets the cancer specific genes,proteins or the tissue environment
that contributes to cancer growth and survival
• Proteasome inhibitors
• Bortezomib
• Histone deacetylase inhibitors
• Panobinostat
• Monoclonal antibodies
• Elotuzumab
• Daratumumab
33. BONE MODIFYING AGENTS
• BISPHOSPHONATES
1. Pamidronate
90 mg iv over 2 hours every 3 – 4 weeks
2. Zoledronic acid
4 mg iv over 15 minutes every 3 – 4 weeks
S/E
1. Renal toxicity
2. Osteonecrosis of jaw
• DENOSUMAB- RANKL inhibitor
34. 2. BONE MARROW STEM CELL
TRANSPLANTATION
• 2 TYPES
1. Autologous- patients own stem cell
2. Allogenic-Donated stem cell
35. 3. RADIATION THERAPY
• Patients with bone pain when chemotherapy is not effective
• Not a disease directed treatment
• Used to treat bone disease if there impending or actual pathological
fractures
4. SURGERY
36. 5. SUPPORTIVE CARE
• Prevention and treatment of infections
• Monitoring,Prevention and management of complications
• Transfusions
