THALIDOMIDE AND DEXAMETHASONE IS AN EFFECTIVE SALVAGE REGIMEN FOR MYELOMA PATIENTS
RELAPSING AFTER AUTOLOGOUS TRANSPLANT
A.Palumbo, P. Falco, M.T. Ambrosini, T. Caravita*, P. Musto*, M. T. Petrucci*, P. Pregno*, I. Avonto, A. Bertola, S. Bringhen, F. Cavallo, G. Ciccone° and Mario Boccadoro.
Divisione di Ematologia dell'Università di Torino - Azienda Ospedaliera S. Giovanni Battista, Ospedale Molinette ­Torino - Italy; the Italian Multiple Myeloma Study Group*;
Epidemiologia dei Tumori, Azienda Ospedaliera S. Giovanni Battista, Ospedale Molinette - Torino - Italy°
ABSTRACT
MATERIAL AND METHODS
Table IB. Patients Characteristics
Figure III. OS from relapse
TD
AT
CC
BACKGROUND: High-dose therapy followed by autologous stem cell transplantation (AT) is the standard treatment for newly
diagnosed multiple myeloma patients. Which is the best treatment option for patients relapsing after AT has not been defined. To
address this issues the efficacy of Thalidomide and Dexamethasone (TD), AT and Conventional Chemotherapy (CC) was evaluated.
Study design: retrospective analysis
2-MG (median ­ mg/l)
3.3
3.6
3.7
MATERIAL AND METHODS: We retrospective analysed the outcome of 90 multiple myeloma patients, median age 61, range 34-
p< 0.008
77, who received a first salvage treatment between January 1999 and September 2003. All patients received AT at diagnosis. Relapse
was defined as introduction of therapeutic modality that was different from maintenance treatment.
M-protein class ­ no(%)
After a median time from diagnosis of 32 months, 43 patients were treated with TD (Thalidomide 100 mg/day associated with DEX
Patient population
40 mg on days 1-4 each month), after a median time from diagnosis of 29 months, 28 patients were treated at first relapse with AT
IgG
24 (56%)
11(39%)
12 (63%)
90 MM patients treated at diagnosis with AT and then salvaged
(86% single MEL100, 11% double MEL100, 4% single MEL200), and after a median time from diagnosis of 32 months, 19 patients
TD
IgA
9 (21%)
9 (32%)
3 (16%)
were treated with CC (32% Doxorubicin, Cyclophosphamide, Etoposide, Cisplatinum combination chemotherapy, 26% Doxorubicin
between January 1999 and September 2003
BJ
9 (21%)
6 (21%)
3 (16%)
containing regimens, 26% Cyclophosphamide containing regimens, 11% other therapies).
Data were analysed when the median follow-up from the start of salvage TD was 30 months (range 4.5-45), from the start of salvage
Others
1 (2%)
2 (7%)
1 (5%)
AT was 18 months (range 3.5-24) and from the start of salvage CC was 21 months (range 2-19.5).
End points of the study were response, progression free survival (PFS) from first relapse and overall survival (OS) from first relapse.
Treatment at diagnosis
RESULTS: Patients characteristics were similar among different groups. At relapse the response rate after TD was: 19% near
Median Time from Diagnosis
complete remission (nCR)(absence of M-Protein detected by electrophoresis), 28% partial response (PR) (M-Protein reduction 50-
99%), 35% stable disease (SD) (M-Protein reduction 0-49%) and 19% progressive disease (PD). After AT was: 11% nCR, 71% PR,
- Tandem MEL100 (melphalan 100 mg/m²) in 62 patients;
and Salvage Treatment (months)
32
29
32
CC
11% SD, 7% PD; and after CC was: 16% PR, 32% SD and 53% PD. Response rate was significantly lower for patients receiving
- Tandem MEL200 (melphalan 200 mg/m²) in 20 patients;
salvage CC in comparison with AT and TD (p<0.001). The median PFS from relapse was 20.3 months for TD, 9 months for AT and
AT
4.5 months for CC (p<0.001). The OS from relapse at 50 months was 58% for TD, 13% for AT and 21% for CC (p = 0.008). The
- Single MEL100 in 6 patients;
median OS from diagnosis was 116.34 months for TD, 41.3 months for AT and 59.5 months for CC (p<0.001).
Median Follow-up from start
The multivariate analysis indicates that TD, 2microglobulin and age were the only independent risk factors associated with
- Single MEL200 in 2 patients.
of Salvage Treatment (months)
30
18
21
improved outcome.
months
CONCLUSION: In conclusion, TD improved PFS and OS in myeloma patients relapsing after autologous transplant.
Salvage treatment
Table III. Multivariate analysis
RESUL
SULTS
BACKG
BAC
R
KGROUND
· TD: Thalidomide 100 mg/die + Dexamethasone 40 mg day 1-4
Variable
Estimated HR (95% CI)
p
each month;
Table II. Clinical Response
PFS from relapse
Therapy
High-dose therapy followed by autologous stem cell transplantation
TD
AT
CC
p
CC
1
· AT: - Single MEL100 in 24 patients;
(AT) is the standard treatment for newly diagnosed multiple myeloma
AT
0.52 (0.27-1.02)
0.06
- Single MEL200 in 1 patient;
TD
0.15 (0.07-0.29)
<0.0001
patients aged 65 or less.
- Tandem MEL100 in 3 patients;
nCR
8 (19%)
3 (11%)
0
0.11*
Age (years)
PR
12 (28%)
20 (71%)
3 (16%)
<0.001**
60
1
SD
15 (35%)
3 (11%)
6 (32%)
> 60
1.18 (0.86-1.61)
0.30
No definitive data are available to define the best treatment option for
PD
8 (19%)
2 (7%)
10 (53%)
· CC: - D-PACE (Doxorubicin + Cyclophosphamide + Etoposide +
MM patients relapsing after AT:
OS from relapse
Cisplatinum) in 6 patients;
* CR vs PR+SD+PD
Therapy
- CC is widely employed with different chemotherapeutic approaches;
- Doxorubicin regimens in 5 patients;
** CR+PR vs SD+PD
CC
1
- AT is effective in management of relapse especially in patients with
- Cyclophosphamide regimens in 2 patients.
AT
1.26 (0.56-2.87)
0.57
Abbreviations
TD
0.37 (0.16-0.86)
0.02
low risk factors ;
nCR = near complete remission (absence of M-Component on electrophoresis)
Age (years)
- Thalidomide in combination with dexamethasone (TD) has proved
PR = partial remission (M-Component reduction 50-99%)
60
1
> 60
1.53 (1.02-2.29)
0.04
effective in advanced myeloma.
SD = stable disease (M-Component reduction 0-49%)
PD= progressive disease
OBJECTIVES
Table IA. Patients Characteristics
CONCLU
LUSIONS
TD
AT
CC
Figure II. PFS from relapse
Compare salvage treatment with TD, AT and CC in patient relapsing
Number of patients
43
28
19
after AT
Response rate after TD is slightly lower than after AT but PFS is
p< 0.0001
significantly prolonged: at relapse good cytoreduction is not enough
Age at diagnosis -year
Median age
58
57
61
to obtain long remission;
Range
(37-71)
(33-70)
(40-71)
TD regimen include maintenance treatment with thalidomide that can
End points of the study:
Sex ­ no(%)
explain the prolonged remission;
Male
25 (58%)
15 (54%)
12 (63%)
- response to salvage treatment;
Female
18 (42%)
13 (46%)
7 (37%)
TD is effective as first salvage approach for MM patients relapsing
- PFS from first relapse;
after AT: it significantly prolonged PFS and OS from first relapse;
Stage ­ no(%)
- OS from first relapse.
TD
IIA
15 (35%)
7 (25%)
6 (32%)
AT
IIB
2 (5%)
1 (4%)
1 (5%)
IIIA
20 (47%)
17 (61%)
10 (53%)
CC
A prospective randomised trial is needed to address this issue.
IIIB
6 (14%)
3 (11%)
2 (11%)
months
DI
DIVI
VISION
SIONE UNI
UNIVERS
VER IT
SITARIA
RIA DI
DI EM
EMATOL
OLOGI
OGIA
AZIENDA OSPEDALIERA S. GIOVANNI BATTISTA
TORINO, ITALY

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