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Perth Haematology :: Dr Steven Ward

Myeloma and Plasma Cell Disorders

 MGUS     Therapy Algorithm      Uniform response criteria (2006)      

MULTIPLE MYELOMA                                    Waldenström's Macroglobulinaemia   Amyloid

 

Myeloma is a cancer of the bone marrow plasma cells. The characteristic features are lytic bone lesions (fractures), accumulation of plasma cells and the presence of a paraprotein (abnormal monoclonal antibody).


PCs

Plasma cells in the marrow are part of the immune system. These cells produce antibody (to help kill invading bacteria).

 

DIAGNOSIS

§         The diagnosis relies on a cluster of features; as the individual features may be seen in other disorders

§         Paraproteins can be seen in lymphoma, Waldenstrom’s macroglobulinaemia, CLL, Primary Amyloid, heavy chain disease, CHAD or less commonly transiently.

§         Lytic bone lesions and fractures can be seen in solid tumours invading bone – prostate cancer or breast cancer

 

§         Myeloma requires:

§         Increased plasma cells in the marrow

§         Paraprotein (in serum or urine)

§         Bony lesions

 

TREATMENT

General measures:

§         Renal failure requires rehydration and treatment for gout

§         Hypercalcaemia (high serum Calcium) requires iv fluids, diuresis, and drugs to reduce the calcium (often biphosphonates – Aredia, Zometa, Bonefos)

§         Bone compression of the spine and spinal cord requires urgent neurosurgery, steroids and radiotherapy / chemotherapy

§         Bone pain due to lytic lesions often responds to radiotherapy

§         Anaemia – transfusion

§         Severe recurrent infections – antibiotics, regular immunoglobulin infusions

 

Chemotherapy:

§         The type of therapy will depend on the patient’s age, general health, extent of myeloma and its complications.

§         Palliative therapy: This type of treatment is aimed at reducing or preventing the problems associated with myeloma without causing excessive side-effects of treatment. Treatment is not curative but aimed at providing a decent quality of life. Elderly patients with lots of additional medical problems would be best served by this approach.

§         Standard chemotherapy: This is used to bring the disease under control, but again without the prospect of cure. Substantial remission and good quality of life is often achieved but the disease becomes active eventually.

§         High-dose therapy (Stem cell transplant): This is reserved for younger patients who are fit enough to tolerate the treatment. Even in this group cure is rarely (if ever) achieved, but a long period of good life with the disease being dormant is possible.

 

Drug combinations used in Myeloma (some are used as initial treatment, some later in relapse):

§         Melphalan & prednisolone

§         Cyclophosphamide & prednisolone

§         VAD (Vincristine, Adriamycin and Dexamethasone)

§         CTD (Cyclophosphamide, Thalidomide, Dexamathasone)

§         Dexamathasone alone (high-dose pulsed)

§         Z-Dex (Idarubicin and Dexamethasone)

§         DT-PACE (Dexamethsaone, Thalidomide, carboPlatin, Adriamycin, Cyclophosphamide, Etoposide)

§         Thalidomide alone

§         Newer agents: Lenalidomide, Bortezomib (Velcade) are in clinical trials currently.

 

Stem cell transplantation is usually performed after 4 cycles of VAD chemotherapy; stem cells are mobilised using high-dose cyclophosphamide and G-CSF; then the myeloablative therapy is high-dose melphalan. See the section on Stem Cell Transplantation.

 

Prognosis

Outcomes are improving with the improvements in detecting disease, managing the complications of the disease as well as better drugs to treat the disease. The median survival is now 3 years (bear in mind many people with myeloma are elderly, with a short survival anyway), and extended with high-dose therapy.

Myeloma is not curable, but 70-90% of patients will respond well to initial treatment, with 40-50% achieving a complete response (no measurable disease). However relapse is inevitable. The time between treatment and relapse is good time without symptoms or problems usually. The timing of the relapse is highly  variable. 15% of myeloma patients are alive after 10 years.

 

 

International Staging System for Multiple Myeloma

JCO 23:3412-3240; 2005  

Stage

Criteria

Median Survival (months)

I

ß2M <3.5mg/L    Albumin >35g/L

62

II

Not Stage I or III

44

III

ß2M ≥ 5.5mg/L

29

For Stage II: ß2M <3.5 but alb <35   OR   ß2M 3.5-5.5 irrespective of alb.

 

 

Recognised Prognostic Factors

Factor

Significance

Clinical

Age

PS

 

Younger – better

Low level – poor

Routine lab tests

B2M

Serum albumin

Serum creatinine

LDH

CRP

Hb

Platelets

 

Higher - poorer

Lower – poorer

Elevated – poor

Elevated – poor

Elevated – poor

Low – poor

Low – poor

Specialised tests

Plasma cell labelling index

Plasma cell morphology

BM cytogenetics/FISH

Microarray

Whole body PET

 

High – poor

Plasmablastic – poor

Hypodiploid / del 13 – poor

Differential patterns

Extramedullary disease - poor

 

Cytogenetic / FISH abnormalities & prognosis

Lower risk High risk
t(11;14) ; t(6;14)
associated with upregulation of Cyclin D1 and D3
t(4;14)
Hyperdiploidy t(14;16) t(14;20) t(8;20)
MAF upregulation
  Inactivation of p53 (17p13)
  del 13

 

MYELOMA  DIAGNOSIS

#

Criteria – all 3 required

1

Monoclonal plasma cells in marrow >=10% and/or biopsy proven plasmacytoma

2

Monoclonal protein present in serum and/or urine [If non-secretory 30% BM PC reqd]

3

Myeloma-related organ dysfunction (1 or more):

C: Calcium elevation

R: Renal failure

A: Anaemia Hb <100g/L or 20g<normal

B: Bon  B: lytic lesions or osteoporosis [If solitary plasmacytoma or osteoporosis alone need 30% BM PC]

 

MGUS DIAGNOSIS

#

Criteria – all 3 required

1

Low level of serum/urine paraprotein: IgG <30g/L, IgA <20g/L K or L < 1.0g/24hr

2

Monoclonal marrow plasma cells <10%

3

Normal Ca2+, Hb, creationine

No bone lesions on skeletal survey / other imaging

No clinical or laboratory features of amyloidosis or light-chain disease

 

 

Smouldering (indolent) Myeloma Diagnosis

(=Stage 1A Durie/Salmon)

#

Criteria – all 3 required

1

Paraprotein required in serum and/or urine

2

Monoclonal plasma cells present in marrow and/or tissue biopsy

3

Not meeting criteria for MGUS, multiple myeloma or solitary plasmacytoma

 

Solitary Plasmacytoma of bone diagnosis

#

Criteria – all 3 required

1

Biopsy-proven monoclonal plasmacytoma of bone in single site. Imaging must be normal outside the site

A low paraprotein may be present (see MGUS levels)

2

Marrow plasma cells < 10%

3

No other myeloma-related organ dysfunction