Haematologica 2003 - Supplements

patients, light chain in 1 patients and 1 patient was diagnosed of
non-secretor myeloma. At the onset of THAL, 2 (15%) patients
were in complete remission (CR), 3 patients (23%) in partial
response (PR) and 8 patients (62%) were refractory to treatment.
Four patients had mass tumoral previously. Response was
assessed by monoclonal protein quantitation in serum or urine,
bone marrow plasma cells percentage and mass tumoral
disappearance. Parameters as hemoglobin level, neutrophils and
platelets ciphers before and after THAL, side effect were
evaluated.
RESULTS: CR was seen in 4 patients(37%), PR was achieved in
5 patients(45%) and 2 patients (18%) were refractory to
treatment. Comparing to the state of disease at the onset of
THAL, 44% of obteined response should be attributable to this
drug. Two deaths were registered before evaluation (in one
patient infection was the cause and in the other was progression
of MM). Two responding patients (18%) had relapsed after
evaluation in a extramedullar mode and died due to myeloma
progression; both of them had tumoral mass previously to THAL
treatment. Median of following up was 11 months (range 4-22).
Although side effects with THAL were frequent (69%), they were
nearly always mild and reversible beeing of grade 1 or 2 degrees
(fatigue, sedation, numbness, unsteadiness). Only one patient
required cessation of THAL due to intolerance. Concerning
blood count, lower neutrophils ciphers had been observed after
THAL treatment although no significative difference was
observed(median of group before THAL was 2.6 x 109/L vs 2,2
x109/L after THAL).
CONCLUSIONS: In our experience THAL alone or with
dexamethasone is a good alternative as salvage therapy in
patients with refractory myeloma without severe side effects.
In patients with high tumoral burden this treatment should be
completed with others therapy strategies.
317
Combination therapy with thalidomide plus oral
melphalan compared with Thalidomide alone for
advanced multiple myeloma
M. Offidani, M. Marconi, L. Corvatta A. Olivieri, §M.
Catarini, #A. Mele °M. Brunori, *M. Candela, L. Malerba, D.
Capelli, M. Montanari, S. Rupoli, , P. Leoni
Clinica di Ematologia and*Clinica Medica, University of Ancona,
Italy#Division of Hematology S. Salvatore Hospital, Pesaro,
Italy§Division of Medicine, Macerata Hospital, Italy°Division of
Medicine, Fano Hospital, Italy
To date, few therapeutic options are available for patients with
relapsed MM, especially when the relapse occurs after stem cell
transplantation. In this context, several trials demonstrated that
thalidomide alone or in combination with dexamethasone
produce response rates of about 30% and 50%, respectively. We
report our experience using a combination of thalidomide and
oral melphalan compared with thalidomide alone in a casecontrol
study including patients with advanced MM.
From May 2000 to July 2002, 27 patients were treated with
thalidomide plus oral melphalan (TM group) and 23 patients with
thalidomide alone (T group). Patients were not excluded because
of either poor performance status or cardiopulmonary, renal and
liver disfunctions. The initial dose of thalidomide was planned to
be 100 mg p.o. daily at bedtime, escalated weekly by 100 mg
increments until a maximum dose of 600 mg daily continuously
until side effects or disease progression were documented.
Melphalan was administered intermittently at a dose of 0.20
mg/kg/d orally for four days every 28 days for almost one course
after greatest response or until severe toxicity. No patients
received antithrombotic prophylaxis.
Prognostic features such as 2-microglobulin, hemoglobin level,
prior regimens, prior high-dose therapy and disease history did
not significantly differ between the two groups of patients while
age was significantly lower in the TM group (69 vs 74 years; p =
0.042) and median follow-up was significantly longer in the TM
group (13 vs 10 months; p = 0.022). Rate of paraprotein decrease
≥ 50% was significantly higher in the TM group compared with T
group (63% vs 26% p = 0.009). Remarkably, ≥ 75% paraprotein
decrease was obtained in 4 patients (15%; ¾ true CR) of TM
patients compared with only 1 (4%; no true CR) of T group. The
median time to remission was significantly shorter in the TM
group (4 weeks vs 7 weeks; p= 0.0312). Multivariate analysis
selected only TM therapy (p = 0.008) as factor associated with
better response. After a median follow-up of 13 months (range 6-
32), 18 patients (36%) had disease progression and 11 (22%)
died. Eight patients died of disease progression, and 1 patient
died for pulmonary embolism, infection and hearth failure,
respectively. PFS was significantly longer in TM group compared
with T group (median NR vs 13 months; 61% vs 45% at 2 years;
p= 0.0356) whereas OS did not most likely because of a median
follow-up significantly shorter in the T group. In the multivariate
analysis only response ≥ 50% was associated with higher PFS at
two years (66% vs 42%; p= 0.0464) and only Hb ≥ 10.5 mg/dl
significantly affected longer OS (76% vs 49% at 2 years; p=
0.0449).
Fourteen patients (28%) stopped and 24 (48%) reduced
thalidomide because of side effects. In the TM group, 4 patients
(15%) delayed the administration of melphalan because of
hematologic toxicity. The main side effects attributable to
thalidomide were constipation (72%), somnolence (38%),
asthenia (24%) and sensory peripheral neuropathy (44%). This
latter adverse event was cause of thalidomide withdrawal in 7
patients (14%). Central nervous system adverse effects
(dizziness, numbness, headache) were found in 8 patients (16%)
although severe toxicity was rare. No differences were found
between the two groups with respect to the above side effects
while rate of deep venous thrombosis (11% vs 4%; p = 0.614)
and grade 3 (WHO) leukopenia (30% vs 13%; p= 0.073) were
higher in the TM group.
This study suggests that oral melphalan added to thalidomide
improves response rate and PFS in advanced poor prognosis
multiple myeloma without increasing severe toxicity.
Consequently, combination of thalidomide plus oral melphalan
should be further investigated in the context of controlled studies.
318
Thalidomide in Relapsed/Refractory Multiple Myeloma:
Experience of a Single Center
G. Esteves, J. Raposo, C. Martins, C. Lopes, J. Lacerda, J.
Alves Carmo, J. M. Forjaz Lacerda
Haematology-Day’s Hospital, Hospital de Santa Maria, Lisboa,
Portugal
Background: Thalidomide (THAL) has significant activity both
as a single agent and in combination with other therapies in
patients with de novo and advanced multiple myeloma. We
presented our results treating advanced disease with THAL alone
or in combination.
Methods: We treated patients with relapsed/refractory myeloma
using dose-escalated THAL up to maximum dose of 800 mg/day.
THAL was given orally for 2 weeks at 200 mg/d, increasing of
200 mg/day each 2 weeks if tolerated. In those patients with no
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