Shared Decision Making in Multiple Myeloma
Implementing
Plasma
cell myeloma
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 Variants
m




Non - secretory myeloma
Indolent myeloma
Smouldering myeloma
Plasma cell leukaemia
 Plasmacytoma
 - Solitary plasmacytoma of bone
 - Extramedullary plasmacytoma
 Immunoglobulin deposition diseases
 - Primary amyloidosis
 - Systemic light and heavy chain deposition disease
 Osteosclerotic myeloma (POEMS)
 Heavy chain diseases

γHCD

αHCD

µHCD
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Multiple Myeloma
Malignant proliferation of plasma cells.
•
•
•
Normal plasma cell form Ig which contain heavy and light
chain
Normal variety of Ig polyclonal & each contain Kappa &
Lambda light chain
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•
•
•
Myeloma plasma cell : Ig of single heavy and light chain
lead to monoclonal protein (para protein)
In some light chain may be only produced and appear in
urine as Bence-Jones proteinuria.
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•
•
•
Incidence : 4 new cases/100,000 peoples/year.
→
Sex ratio : M:F
2:1
Age : median age 60-70 years.
Etiology : Unknown,chemical, enviromental
Implementing Shared Decision Making in Multiple Myeloma
Classification of MM
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Paraprotein
IgG
frequency %
55%
IgA
Light chain only
Other (D, E, non secretory)
21%
22%
2%
The diagnosis of MM requires two of the following
 marrow plasmacytosis.
 Serum and/or urinary paraprotein

+

≥ 1 of `` CRAB``
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MM: Clinical Manifestations
Series of genetic mutations, translocations, normal cell turns malignant
Hallmarks of myeloma: CRAB (also known as myeloma defining
events;MDE)
R = Renal
Complications
C = Hypercalcemia
Recurrent infections*
A = Anemia
* Not
an MDE, yet relatively common
Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-e548.
B = Bone
Disease
Implementing Shared Decision Making in Multiple Myeloma
Multiple Myeloma
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Pathology
Effect
Symptoms
Marrow involvement with
malignant plasma cell
Bone erosion due to
stimulation of oesteoclast.
Pathological fracture
Pain
Hypercalcaemia
BM failure
Excess production of light
chains and paraprotein
Renal damage
Increased blood viscosity
Amylidosis -renal damage
Reduction in number of
normal plasma cells
Impaired immune function
Severe local pain
Lethergy,
thirst
Anaemia&
tiredness
Infection (Resp.)
Clinical features
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•
•
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Weight loss ,malaise and fatigue.
Bone pain found in 60% of cases at the back and ribs.
Anorexia , diarrhea, vomiting, constipation, polyuria,
polydipsia occur with hypercalcemia in 30%,
Renal impairment due to hypercalcaemia and dehydration
present in 50% .
Pneumococcal, chest and urinary tract infection due to low
immunoglobulin(Ig) production.
Headache , Confusion, Breathlessness, Visual Disturbance
and bleeding can occur secondary to hyperviscosity (IgA).
5% present with paralysis secondary to spinal cord
compression by extra-dural plasma cell mass.
Carpal-tunnel syndrome, nephrotic syndrome, cardiac
failure and neuropathy secondary to amyloid deposition.
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Implementing Shared Decision Making in Multiple Myeloma
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• Absence of immunoparaesis should cast doubt on diagnosis.
• Only about 5% of pts with ESR persistently above 100 mm in the 1st
hour have meyeloma.
Implementing Shared Decision Making in Multiple Myeloma
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Revised IMWG Criteria (2014)
Republished with permission of American Society of Hematology, from Ghobrial, IM, et al. How I treat smoldering multiple
myeloma, Blood. 2014;124:3380-3388; permission conveyed through Copyright Clearance Center, Inc.
Best Practices in Multiple Myeloma
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Initial Approach to Treatment of Myeloma
Nontransplant Candidate
(based on age, performance
status, and comorbidities)
Transplant
Candidate
Induction treatment
Induction treatment
(4-6 cycles)
Maintenance
Stem cell harvest
Stem cell transplantation
Consolidation therapy?
Maintenance
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Increased Treatment Options in MM
MM Therapies
Introduction
1950
1960
1970
FDA Approved in MM
1980
1983
Autologous
transplantation
1958
Melphalan
1962
Prednisone
1969
Melphalan +
prednisone
1986
High-dose
dexamethasone
1990
2000
2003
Bortezomib 3rd line
2005
Bortezomib 2nd line
2006
Lenalidomide + dex
2nd line;
Thalidomide + dex
1st line
2007
Doxorubicin +
bortezomib
2nd line
2010
2015
2008
Bortezomib
frontline
2012
Carfilzomib
3rd line; Bortezomib SC
2013
Pomalidomide 3rd line
2014
Bortezomib
retreatment
2015
Panobinostat 3rd
line; Lenalidomide
1st line
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Supportive Care
 Bone: 85% will develop bone disease
– All should receive monthly bisphosphonates after dental
exam; monitor renal function long term
 Infection: major cause of death in MM
– Impaired antibody formation after antigenic stimulations
– Immunizations: pneumococcal (PCV13, PPSV23), seasonal
inactivated influenza
– Shingles prophylaxis (proteasome inhibitor, transplant)
 Renal: monitor status, dose reductions may be necessary
– Acute renal failure can occur due to NSAIDs, CT dyes,
antibiotics
– Hydrate (carefully), monitor monthly
Bilotti E, et al. Clin J Oncol Nurs. 2011;15(suppl):5-8. Miceli TS, et al. Clin J Oncol Nurs. 2011;15(suppl):9-23.
Faiman B, et al. Clin J Oncol Nurs. 2011;15 66-76. MMWR. 2014;46:1-24.
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ManagementCont…
• Allopurinol to prevent urate nephropathy.
• Plasmapheresis, if necessary, for hyperviscosity
**Chemotherapy with or without HSCT
In older patients, thalidomide combined with the alkylating agent
melphalan and prednisolone has increased the median overall survival
to more than 4 years.
In younger, fitter patients, standard treatment includes first-in
chemotherapy to maximum response and then an autologous HSCT
Implementing Shared Decision Making in Multiple Myeloma
Cont.-Management
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1-BORTEZOMIB(VELCADE)
VTD+Z
2- Thalidomide
3-Lenalidomide(Revlimid)
VRD+Z
4- Dexamethasone
5-Bisphosphonate (Zoledronate)
Treatment is administered until paraprotein levels have stopped falling. This is
termed‘plateau phase’ and can last for weeks or years.
Radiotherapy; for localised bone pain and for pathological fractures.
It is also useful for the emergency treatment of spinal cord compression
complicating extradural plasmacytomas
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Long-term Effects of Treatment
 Diarrhea (lenalidomide)
 Peripheral neuropathy (bortezomib, MM, diabetes)
 Secondary cancers
 Cardiovascular/pulmonary disease
– Health maintenance is important as patients are at risk for
same illnesses as those without MM
 Financial
– Chronic illnesses are costly
– Loss of income, hospital and medical bills can be high
Refer to patient care organizations, copay foundations
Faiman B. J Adv Pract Oncol. 2013;4:354-360. Kurtin S, et al. Clin J Oncol Nurs. 2013;17(suppl):7-11.
Faiman B, et al. Blood. 2013;122:5397.
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Waldenstrӧm
macroglobulinaemia
This is a low-grade lymphoplasmacytoid lymphoma
associated with an IgM paraprotein.
Patients classically present with features of
hyperviscosity,such as nosebleeds, bruising, confusion and
visual disturbance.
Anaemia, systemic symptoms, splenomegaly or
lymphadenopathy
Investigation; have an IgM paraprotein associated with a
raised plasma viscosity. The bone marrow with infiltration of
lymphoid cells and prominent mast cells.
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TREATMENT
1-Plasmapheresis for anaemia and hyperviscosity.
2- Chlorambucil
3- Fludarabine
4- Rituximab
*Monoclonal gammopathy of uncertain significance (MGUS);
a paraprotein is present in the blood but with no other features of myeloma,
Waldenstrӧm macroglobulinaemia, lymphoma or related disease.
The bone marrow may have increased plasma cells but these usually constitute
less than 10% of nucleated cells.
After follow-up of 20 years, only one-quarter of cases will progress to myeloma
or a related disorder (i.e.around 1% per annum)