Case Management Experience in Multiple Myeloma

Name : Prof. DR. Dr. Arry Harryanto Reksodiputro, SpPD-KHOM

Posisi : Divisi Hematologi-Onkologi Medik Bagian Ilmu Penyakit Dalam FKUI-RSUPNCM

Pendidikan
 1963 : Fakultas Kedokteran Universitas Indonesia
 1969 : Spesialis Ilmu Penyakit Dalam, Fakultas Kedokteran Universitas Indonesia
 1970 : Pendidikan Hematologi di Rumah Sakit St. Louis, Universitas De Paris, Perancis
 1978 : Pendidikan Teknik Membrane Marker pada Imperial Cancer Research Fund,
Department of Medical Oncology, St. Bartholomew’s Hospital, London
 1979 : Pendidikan Sitologi Limfoma Malignum pada The Hospitalier Pitie-Salpetriere,
Paris
 1984 : Doktor pada Fakultas Kedokteran Universitas Indonesia-Universitas Leiden
 1991 : Guru Besar pada Fakultas Kedokteran Universitas Indonesia
Case Management Experience in
Multiple Myeloma

A.HARRYANTO REKSODIPUTRO
SRI AGUSTIN

SUB BAG HEMATOLOGI ONK

MEDIK
FKUI,RSCM,RSKD
2
Patients’ Characteristic (N=14)
N %
<65 6 42.86
Age
>=65 8 57.14
Male 6 42.86
Gender
Female 8 57.14
IgG 4 28.57
IgA 3 21.43
Heavy chain type
LCD 1 7.14
NA 6 42.86
≥10 2 14.29
Hb <10 11 78.57
NA 1 7.14
<70000 2 14.29
Platelet ≥70000 11 78.57
NA 1 7.14
Yes 10 71.43
Bone lesions No 1 7.14
3
NA 3 21.43
 Patients’ >=2.0
N
3
%
21.43
Characteristic NA
<3.5
2
6
14.29
42.86
(N=14) Serum albumin >=3.5
NA
7
1
50
7.14
<3.5 3 21.43
3.5-5.5 1 7.14
Serum B2M
>5.5 4 28.57
NA 6 42.86
<30% 2 14.29
30-70% 7 50
Plasma cells of BM
>70% 1 7.14
NA 4 28.57
I 3 21.43
II 1 7.14
ISS Staging
III 4 28.57
NA 6 42.86
IIA 4 28.57
IIIA 5 35.71
Durie Salmon Staging
IIIB 3 21.43 4
 FRONTLINE THERAPY OPTIONS
OPTIONS COMMENTS

Melphalan/prednisone Still an option, especially for elderly people

Alkylating agent combinations Really only an option if stem cell transplant
is not planned
Cytoxan alone or in combination Can be useful alone or in combination with
less stem cell injury than melphalan

VAD regimen Still a major frontline approach; can have

significant disadvantages

Dexamethasone or other steroid alone A valid option, especially with renal

insufficiency and/or blood count values

Thalidomide plus Dexamethasone A new oral option worthy of consideration

but without a long track record

Bortezomib plus Dexamethasone, or in A novel agent, option if stem cell transplant

combination with other agents is planned, option if there’s renal
insufficiency 5
 Choice of Therapy
Bortezomib-based Non bortezomib-based
regimen regimen
First line therapy, 3 patients 11 patients
(in newly diagnosed
Multiple Myeloma)

Salvage therapy (in 4 patients

Relapsed/refractory
Multiple Myeloma)

7
 RECOGNIZED PROGNOSTIC FACTORS2
Factor Significance
Specialized tests

Plasma cell labeling index High-poor

Plasma cell morphology Plasmablastic-poor
Bone marrow cytogenetics

Standard cytogenetics Hypodiploidy/deletion 13-poor

FISH analysis (chromosome 13) 13 deletion-poor
Microarray techniques Differential patterns
Whole-body FDG/PET scan Extramedullary-disease poor
8
 Range time of Survival
1st year 2nd year 3rd year 4th year 5th year 6th year 7th year

14

13

12

11

10

9
Patient

0 10 20 30 40 50 60 70 80 90 100
Months
Bortezomib-based first line
Non bortezomib-based first line
Non bortezomib-based as first line, Bortezomib-based as salvage 9
 Survival (Bortezomib vs Non-Bortezomib)
Survival times (months)
Bortezomib Vs Non Bortezomib

III B

III A

III A

III A

II A

NA

II A

III B

III B

III A

III A

NA

II A

II A

0 10 20 30 40 50 60 70 80 90 100
10
 Note for Range time of Survival
• Patients didn’t start the treatment at the same
time
• Bortezomib as salvage therapy seemed could
prolong the range time of survival
• Bortezomib as first line therapy looked like not
having very long range time survival, but the
patients actually are new and still on going
and others are using Bortezomib in short
period due to financial reason

11
 Durie Salmon Staging
B

NB than B

NB than B

NB than B

NB

NB
Patient

NB

NB

NB

NB

NB

NB than B

0 10 20 30 40 50 60 70 80 90 100
Months
Stadium IIA
Stadium IIIA
Stadium IIIB 12
Not applicable
 Role of Stage in Survival Bortezomib vs
Non Bortezomib Pts
Survival times (months)
Bortezomib Vs Non Bortezomib

III B

III A

III A

III A

II A

NA

II A

III B

III B

III A

III A

NA

II A

II A
13
0 10 20 30 40 50 60 70 80 90 100
 Note for Durie Salmon Staging
• Patients didn’t start the treatment at the same
time
• Two patients staging are not applicable
because criteria is not complete
• The staging seemed not really influence the
range time of survival, as it’s not the only
factor that determine patient’s survival
• Bortezomib are used in all staging

14
 Quality of Life
B

NB than B

NB than B

NB than B

NB

NB
Patient

NB

NB

NB

NB

NB

NB than B

0 10 20 30 40 50 60 70 80 90 100
Good QoL Months

Poor QoL
15
 Quality of Life
Survival times (months)
Good QoL vs Poor QoL

Bortezomib

Bortezomib

Bortezomib

Bortezomib

Bortezomib

Bortezomib

Bortezomib

Non B

Non B

Non B

Non B

Non B

Non B

Non B

0 10 20 30 40 50 60 70 80 90 100

Good QoL
16
Poor QoL
 Note for Quality of Life
• Patients didn’t start the treatment at the same
time
• Criteria for good or poor quality life is based on
the patients condition and history of
hospitalization
• Most patients used Non-bortezomib based
regimen only, had poor quality of life, disease
progression, and died
• More patients used Bortezomib-based regimen
(as first line, or salvage) had good Quality of Life
17
PATIENTS HISTORY OF TREATMENT

18
 Patient 1
• Male CD, 65 yrs, IIIB, (anemia, hypercalcemia,
renal impairment, bone lesions)
Oct 2014
Diagnosed as Multiple
Myeloma,
Symptoms: low back
pain, postural
dizziness, renal Jan, 2015
impairment Using TP regimen

Nov-Dec 2014 March 2015

Used VTD/VT Being hospitalized,
regimen, because anemia,
Outcome: hypercalcemia, acute
hematological tests renal injury
and renal functions
19
are improved
 Patient 2
• Male DS, 77 yrs, Stage NA

Jan, 2010 Sept, 2014 Jan 2015,

Diagnosed as Stop Thalidomide Live,
Multiple maintenance, hematological
Myeloma, progression, tests are
Symptoms: (anemia, bone improved,
anemia lesions, SPEP+, IF+) globulin normal

Apr 2010-Sept Sept-Dec 2014

2014 Used VT
Used TD regimen
regimen,

20
 Patient 3
• Male TW, 60 yrs, IIA

June, 2011 Sept, 2012 Jan 2015,

Diagnosed as Relaps, Live, Relaps,
Multiple Then using
Myeloma, TD/T/TD regimen,
Symptoms: (anemia, bone
waist pain lesions, SPEP+, IF+)

Oct – Dec 2011 Oct 2013

Used VD/V regimen Stop all therapy
4#,
Outcome : Protein
and SPEP become
21
normal
 Patient 4
• Male RBS, 77 yrs, IIIA

Mar, 2008
Diagnosed as Multiple
Myeloma,
Apr, 2009
Symptoms: nosebleed,
gumbleed, melena, Disease progression,
waist pain Dead

Jul 2008
Used MT/MP regimen

22
 Patient 5
• Female JL, 31 yrs, Stad NA

Aug, 2005
Diagnosed
as Multiple
Myeloma,
Symptoms: Jul, 2009 After Jul 2011,
weakness Relaps, Loss to follow-up

Aug 2005 – Jan 2007 Jul 2009 – Jul 2011

Used TD/T regimen Used TD/COP/MT
regimen

23
 Patient 6
• Female MM, 60 yrs, IIIA, hypercoagulation

Oct, 2011
Diagnosed as Multiple
Myeloma, Mar, 2013
Symptoms: limb pain, Dead,
weakness Progressive Disease

Oct 2011 – Dec 2012

Used MTD/MT/MP/COP/D but
irreguler admission due to
nonadherence, patient also used
Herbal

24
 Patient 7
• Female WIH, 65 yrs, IIA
Oct, 2006
Diagnosed as
Multiple
Myeloma, Aug 2007 - .. 2009 Jul, 2010
Symptoms: On vacation to Disease
limb pain, abroad, T stop used Progression,
weakness treatment Dead

Oct 2006 – May 2007 Apr – Sept 2009,

Used COP/C regimen, Used MT
Outcome : Stable regimen
Disease

25
 Patient 8
• Male N, 57 yrs, IIIB, renal impairment

Mar, 2009
Diagnosed as Multiple Feb, 2010
Myeloma, Febrile neutropenia,
Symptoms: waist pain, admissioned at ICU, very bad
renal impairment condition, Dead

Apr 2009 – Jan 2010

Used TD/M/MT regimen

26
 Patient 9
• Female CH, 58 yrs, IIIB, Free light chain disease

Dec, 2009
Diagnosed as Multiple
Myeloma,
Symptoms: limb pain, Mar, 2010
weakness Disease progression, Dead

Dec 2009 – Mar 2010

Used MTD regimen

27
 Patient 10
• Female SL, 65 yrs, IIA

Nov, 2012
Diagnosed as Multiple
Myeloma, Feb 2015
symptom: weakness Live, partial response

Dec 2012 – Sept 2014

Used MP regimen until now

28
 Patient 11
Jun, 2006
Diagnosed
• Male R, 70 yrs, IIIA
as
Multiple
Myeloma,
Symptoms
: low back Oct 2008
pain,
postural Used V .. 2013,
dizziness, regimen, …. Relaps,
renal AE: herpes, 20.., Used TD
impairmen pneumonia, Relap regimen
t neuropathy s

Jun 2006 – …. - …. May-Jul Aug 2013,

….. Used 2011, Disease
Used MT/MP Used V/MD Progression
CTD/COP/CTD regimen regimen , Dead
/MTD Outcome:
regimen, Partial
Outcome: Response,
Stable no AE
disease 29
 Patient 12
• Female R, 69 yrs, IIA
Mar, 2013
Diagnosed as Nov – Dec 2014
Multiple Used Bortezomib Feb 2015,
Myeloma, regimen, Live,
Symptoms: limb Stopped due to Stable
pain, weakness financial reason disease

May 2013 – Sept 2014 Jan 2015

Used COP/MP regimen, Used M regimen
Outcome: Partial
Response

30
 Patient 13
• Female MSH, 51 yrs, IIIA
Aug, 2007
Diagnosed as
Multiple Sept – Oct
Myeloma, Jan 2012 Sept – Jun 2014,
2012, Nov 2013,
Symptoms: Used Disease
coccyx pain, Relap MT/CD/M Used VD Progressio
weakness s D regimen regimen n, Dead

Aug 2007 – Jan – May Jun Apr 2014,

Jul 2011 2012 2013, Relaps,
Used Used Relap Used MD
TD/MP/M Bortezomi s regimen
PT/V/T b regimen
regimen, 6#,
Outcome: Outcome:
Stable Partial
Disease Response

31
 Patient 14
• Female NM, 75 yrs, IIIA

Dec, 2012
Diagnosed as
Multiple Myeloma,
Symptoms: limb Sept 2013 – Dec 2014
pain, weakness Used CP/P regimen,

Sept 2013 Mar 2015

Used VT/V regimen, Live
Outcome: Protein normal,
SPEP normal

32
 Conclusions
• Most patients came with unspecific symptoms,
like pain, weakness
• With patients with anemia, renal impairment,
and bone lesions, think about differential
diagnosis of Multiple Myeloma
• Give therapy that could give longer time of
survival and preserve the good quality of life
• Bortezomib give good result in patient with newly
diagnoses or in relaps/refractory patient, even if
the patient had stadium IIIB and renal
impairment
33