multiple myeloma a new treatment approach

8/8/2019 Multiple Myeloma a New Treatment Approach

1/27

Nugroho Prayogo

Dharmais Cancer Center.


2/27

1. An estimated 20,580 people diagnosed in the UnitedStates in 2009

2. A type of blood cancer in which plasma cells grow

uncontrollably, usually inside the bone marrow

3. Associated with bone lesions that cause structural

damage and/or fractures from overproduction of

myeloma cells

4. Referred to as multiple myeloma because about 90% of

patients have multiple bone lesions

5. Solitary plasmacytoma: a mass of myeloma cells in onesite in the bone or another organ

6. Extramedullary plasmacytoma: myeloma that begins in

other tissues, such as skin, muscle, or lungs

Introduction :

ASCO 2009


3/27

Multiple MyelomaHighly treatableRarely curable, except Solitary plasmacytoma Extramedullary plasmacytoma

Median survivalPre-chemotherapy 7 monthChemotherapy 24 30 monthNewer therapies (Corticosteroid,

Thalidomide, Bortezomib, Lenalidomide,Transplantation (allo/auto) 45 60month

Continou......


4/27

Found inside the

bone marrow

(spongy, red tissue in

the inner part of largebones)

Part of the bodys

immune system that

produce antibodies

to help the body fight

infection


5/27

1. Age

2. Race

3. Exposure to radiation and chemicals

4. History of solitary plasmacytoma

5. Monoclonal gammopathy of unknown significance(MGUS): a low level of a protein called monoclonal

immunoglobulin (M protein


6/27

General Weight loss

Easy bruising

Hazy vision

Bleeding gumsBones

1. Pain

2. Fractures

Hypercalcemia (highcalcium levels in the blood)

Nausea and vomiting

Increased urination

Excessive thirst

Kidney Failure1. Nausea and vomiting2. Fatigue

3. Weakness

Amyloidosis (build-up of proteins)1. Peripheral neuropathy (nerve

damage)

2. Edema (swelling caused by build-upof fluid in the body)

3. Enlargement of organs


7/27

MGUS

< 3 g M spike

< 10% PC

Smoldering MM

3 g M spike

OR: 10% PC

NO anemia & bone lesions;

normal calcium &

kidney function

Anemia, bone lesions,

high calcium, or

abnormal kidney

function

Kyle RA, et al. N Engl J Med. 2002;346:564-569.

Active MM

10% PC

M spike +

AND


8/27

Bone pain: 58%

Fatigue: 32%

Weight loss: 24%

Paraesthesia: 5%

11% are asymptomatic or have only mild

symptoms at diagnosis

Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33.


9/27

1. Increased plasma cells in the bone marrow

(96%)

2.

Monoclonal (M) serum protein (93%)3. Anemia (normochromic normocytic; 73%)

4. Lytic bone lesions (67%)

5. Renal failure, serum creatinine 2.0 (19%)

6. Hypercalcemia (corrected calcium 11)(13%)

7. Infection

Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33.


10/27

1. Blood test for anemia, kidney function, and calcium levels

2. Blood and urine tests to measure M protein levels

3. Bone marrow biopsy

4. Diagnosis is confirmed with a bone marrow biopsy5. X-ray

6. Magnetic resonance imaging (MRI)

7. Computed tomography (CT or CAT) scan

8. Positron emission tomography (PET) scan or PET-CT


11/27

1. Asymptomatic plasma cell neoplasia- MGUS (usually IgG kappa/lambda, IgA kappa/lambda)

2. Symptomatic plasma sel neoplasma(usually IgG kappa/gamma, IgA kappa/gamma)

a. Primarily affecting bone

- Multiple Myeloma (94%)

- Solitary plasmacytoma (3%)b. Extramedullary plasmacytoma (3%)

3. Macroglobulinemia(usually IgM kappa/gamma)- Often have lymphadenopathy and hepatosplenomegaly- less than 5% have lytic bone lesions.

- Lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia.

Ref : Multiple Myeloma and other Plasma Cell Neoplasms Treatment. National Cancer Instititue.http://www.cancer.gov
http://www.cancer.gov/http://www.cancer.gov/http://www.cancer.gov/


12/27

Stadium : dasar penetuan :

ditaksir dari kadar protein myeloma dari serum dan

/urine.

Ditambah beberapa parameter:

Hb, Ca darah, U/cr, jumlah lesi litik, jenis m protein

Stadium : faktor kuat , predictor survival .

tetapi sedikit mempengaruhi terapi

Ref : Multiple Myeloma and other Plasma Cell Neoplasms Treatment. National Cancer

Institute.

http://www.cancer.gov
http://www.cancer.gov/http://www.cancer.gov/


13/27

International Myeloma Working Group : 11.171 kasus (2901 menerima HD terapi ; 8270 menerima SD terapi)

Muncul ,,ISS,, (International Staging System)

2-M = serum 2-microglobulin in mg/dL; ALB = serum albumin in g/dL.

Staging of disease strong determinant of survival.

Stage Criteria Median Survival

Stage 12-M < 3.5 and ALB 3.5 62 month

Stage 22-M < 3.5 and ALB < 3.5

or

2-M 3.5 to < 5.5

44 month

Stage 3 2-M 5.5 29 month


14/27

Mayo clinic : Neoplastic hematology and

Medical oncology; Edited by Ayelew Tefferi

2008

Karyotypic deletion 13 or

hypodiploidy

High plasma cell labeling

index

Molecular genetics: t(4;14),

t(14;16) or 17p- High LDH, 2-M, or CRP

Increased circulating plasma

cells

Plasmablastic morphology

Low albumin

CCOClinical Care Option Multiple

Myeloma

Performance status International Staging System

stage

Conventional cytogenetics

Deletion of chromosome 13

Hypodiploidy FISH = t(4;14), t(14;16) or

del 17p-

Lactate dehydrogenase

Plasmablastic morphology

Plasma cell labeling index

(limited availability)


15/27

Mayo clinic : Neoplastic hematology and Medical oncology; Edited by Ayelew Tefferi 2008


16/27

Most often Expresses IgA lambda

Less often have skeletal-

related complications

Dispenzieri A, et al. Mayo Clin Proc. 2007;82:323-341. v5 Revised and updated: Jan 2009.Fonseca R, et al. Leukemia. 2009; Oct 1. [Epub ahead of print]

*Patients with t(4;14), 2-M


17/27


18/27

Mayo clinic : Neoplastic hematology and Medical oncology; Edited by Ayelew Tefferi

2008

James CS Chim


19/27

James CS Chim


20/27

Induction Steroids (dexamethasone, prednisone) Thalidomide Bortezomib Alkylating agents (melphalan, cyclophosphamide) Lenalidomide Others (vincristine, doxorubicin, liposomal

doxorubicin)

Consolidation Autologus / Allogeneic bone marrow or peripheral

stem cell transplantationMaintenance

Interferon alfa Bisphosphonate

Ref : Multiple Myeloma and other Plasma Cell Neoplasms Treatment. National Cancer

Institute. http://www.cancer.gov
http://www.cancer.gov/http://www.cancer.gov/


21/27

Combination options Melphalan + Prednisone (MP)

Vincristine + Adriamycin + Dexamethasone (VAD)

Bortezomib + Dexamethasone Bortezomib + Melphalan + Prednisone (VMP)

Melphalan + Prednisone + Thalidomide (MPT)

Bortezomib + Thalidomide + Dexamethasone (VTD)

Bortezomib + liposomal Doxorubicin Lenalidomide + Dexamethasone

Bortezomib + Lenalidomide + Dexamethasone

Ref : Multiple Myeloma and other Plasma Cell Neoplasms Treatment. National CancerInstitute.
http://www.cancer.gov/


22/27

Mayo clinic : Neoplastic hematology and Medical oncology; Edited by Ayelew Tefferi 2008


23/27

Regimen Advantages InductionResponse

Post-ASCTResponse

Reference

RD = Lenalidomide,

mod-dose DexaSynergy

ORR 69%

CR unclear

ORR 70%

CR


24/27

IncorporateAutologous BMTwith conventional

chemotherapy to increase CR rate, a requisite

for cure

Maximal eradication of tumor cells prior to autologousBMT theoretically result in least contamination of thestem cell graft, and hence possibly improve outcome

This may be achieved by the incorporation ofBortezomib : a highly effective agent for MM

James CS Chim, ATOM clinical trial.


25/27


26/27

Kemajuan besar (asct)pada terapi MM, terjadi padabeberapa tahun belakangan ini, dengan hasil lebihbaik.

ASCT merupakan standrad terapi bila tidak adakontra indikasi, walau Median Survival tgt prognostic

factors.

Uji klinis direncanakan dengan membandingkanobat-obat baru seperti bortezomib dan lenalidomidepada MM ditujukan pada perjalanan awal penyakit.

Serta dirancang berdasarkan faktor risiko danfaktor prognostik (al.cytogenetic).


27/27

TERIMA

KASIH

Thank You

multiple myeloma a new treatment approach

Documents