Haematologica 2003 - Supplements

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Thalidomide treatment of patients with advanced
multiple myeloma
J.Bila, I.Elezovic, D.Tomin, M.Gotic, B.Mihaljevic,
N.Suvajdzic, M.Sretenovic, V.Cemerikic, D.Boskovic.
Institute of Haematology, Clinical Center of Serbia, Belgrade,
Serbia.
Background: Thalidomide activity in the treatment of advanced
myeloma is confirmed by number of studies. It is administered as
single agent or in combinations with other therapies. The aim of
study was to present results of Thalidomide treatment used in
patients (pts) with advanced myeloma. Patients and methods:
During period November 2001 – January 2003, 11pts (8M/3F,
mean age 57yrs, range 48 – 69yrs) were treated with
Thalidomide. According to the clinical stage of disease,
distribution was as follows: IIA 2pts (18,2%), IIIA 5pts
(45,4%), and IIIB 4pts (36,4%).There were 5pts (45,4%) with
IgG kappa monoclonal protein; 4pts with IgG lambda (36,4%);
1pts with IgA lambda (9,1%); and 1pts with secretion of lambda
light chain (9,1%).Highly elevated Beta2 microglobulin (>3mg/l)
was registered in 8pts (72,7%).Immunohistochemical stainings of
bone marrow biopsy revealed high expression of VEGF and Ki-
67 in 5/6 analyzed pts.
The group consisted of 2pts (18,2%) with refractory disease and
9pts (81,8%) with relapsing myeloma. All the patients were
heavily pretreated with at least three types of conventional
chemotherapy (MP/VMCP, VAD, M2, Z-Dex).
Thalidomide as monotherapy was administered in 7pts (63,6%) at
median dose of 400mg/day (range 200-600mg/day).At the same
dosage, in 4pts (36,4%) Thalidomide was used in combination
with high doses of Dexamethasone (HD-Dexa 40mg/d, I-IVd,
XV-XVIIId for 6 cycles).
Results: Median follow-up was 12m for both pts groups (range 3-
15m).The commonly observed side effects were: neuropathy in
6pts (54,6%), sleepiness in 4pts ( 36,4%), constipation in 1pts
(9,1%) and skin dryness in 2pts (18,2%).No case of deep vein
thrombosis was observed. Responses according to the
EBMT/IBMTR guidelines in 7pts treated with Thalidomide as
monotherapy were: 2 partial responses (28,6%), 3 minimal
responses (42,8%), and 1 stable disease (14,3%).
One patient had a progressive disease (14,3%). In the group of
4pts treated with Combination Thalidomide+HD-Dexa,
distribution of responses was as follows: 1 partial response
(25%), 2 minimal responses (50%) and 1 stable disease (25%).
Median survival was 6,5months (range 3-15m) and one year
survival was registered in 30%pts.
Conclusion: The activity of Thalidomide, used as a single agent
or in combination with Dexamethasone, is significant in the
treatment of patients with advanced myeloma. The optimal dose
is still uncertain and although it has a significant side-effect
profile, Thalidomide is a good prototype of a whole new class of
anti-myeloma agents.
11.2 Thalidomide combinations in refractory MM
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LOW-DOSE THALIDOMIDE AND DEXAMETHASONE
IMPROVES SURVIVAL IN MULTIPLE MYELOMA
PATIENTS.
A. Palumbo, A. Bertola, P.Falco, R.Rosato*, F. Cavallo, S.
Bringhen, L. Giaccone, P. Musto§, P.Pregno, G. Ciccone*
and M. Boccadoro
Divisione di Ematologia dell'Università di Torino, *Epidemiologia
dei Tumori e Centro per la Prevenzione Oncologica dell’Università
di Torino, §Divisione di Ematologia, IRCCS “Casa Sollievo della
Sofferenza”, S. Giovanni Rotondo, Italy,°Divisione di Ematologia
Ospedaliera – Azienda Ospedaliera S. Giovanni Battista, Ospedale
Molinette - Torino – Italy
Oral melphalan and prednisone has been the standard treatment of
multiple myeloma for more than 30 years. High-dose
chemotherapy and autologous stem cell transplantation improves
clinical outcome. Relapses, however, constantly occur and
resistance to chemotherapy is the major cause of death. The search
for new/old drug has led to the selection of thalidomide.
We evaluated the efficacy of low dose thalidomide (THAL) plus
dexamethasone (DEX) in patients with relapsed or refractory
multiple myeloma.
One hundred and twenty patients (median age 63), that had
relapsed or were refractory to chemotherapy, started treatment with
THAL 100 mg/day (continuous) and DEX 40 mg (days 1-4 of each
month) between July 1999 and October 2001. Their clinical
outcome was compared to a control group of 120 patients (median
age 62) selected from relapsed or refractory patients treated with
conventional chemotherapy (CC). Clinical characteristics were
quite homogeneous in the two groups. Results were showed
separately on patients receiving THAL-DEX or CC after one line
of chemotherapy only (early stages of disease), and those treated
after two or more lines of chemotherapy (late stages of disease).
THAL-DEX regimen significantly improved outcome in patients
treated after one line of chemotherapy only. Myeloma protein
reduction 50%-100% was observed in 56% of the THAL-DEX
group and in 46% of the CC group. The probability of progressionfree
survival (PFS) for 3 years was 38 % in the THAL-DEX group
and 6 % in the CC group (p=0.0024). The estimated survival for 3
years was 60% in THAL-DEX group and 26% in CC group
(p=0.0016).
Clinical outcome was similar in patients receiving THAL-DEX or
CC after two or more line of chemotherapy. Myeloma protein
reduction 50%-100% was observed in 46% of the THAL-DEX
group and in 42% of the CC group. The probability of PFS for 3
years was 11% in the THAL-DEX group and 3% in the CC group
(p=0.23). The estimated survival for 3 years was 22% in THAL-
DEX group and 12% in CC group (p=0.45).
Most adverse effects were recorded as WHO grade I, 12% of patients
displayed a grade II toxicity and 4% grade III. Constipation was
relatively frequent (17% of patients). Sedation was recorded in 13%
of patients, and 7% showed confusion. Tingling and numbness were
observed in 11% of patients as grade I, in 8% as grade II. Tremors
and incoordinations were present in 6% of patients and were
generally mild. Discontinuation was required in 18% of patients,
mainly due to neurologic toxicity (11%). In the earlier phases of
disease, THAL-DEX was superior to CC. In the more advanced
stages of disease THAL-DEX was equivalent to CC. This regimen is
not myelotoxic, postpones the delivery of chemotherapy, and
therefore the development of resistant disease, that is the major cause
of death in the more advanced stages of myeloma.
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