Haematologica 2003 - Supplements

time from diagnosis was 3.7 years and the mean number of
previous treatment lines was four. Seven patients had previously
undergone low intensity allogeneic stem cell transplantation
followed by donor lymphocyte infusions,
13 had received autologous stem cell transplantation and 5
patients had only had chemotherapy. Thalidomide was started at a
daily dose of 50 mg and escalated up to the mean dose of 200
mg/day. Dexamethasone was administered at 40 mg p.o daily for
four days monthly, and Cyclophosphamide was given at the
target dose of 400mg/m2 p.o weekly. Thirteen patients with
neutropenia at start of treatment were commenced on G-CSF
support. Eight patients who were transfusion dependent were
commenced on Erythropoietin.
Results: Nine patients developed infections (8 developed chest
infection and one patient developed an abscess, all successfully
treated with iv antibiotics). All patients with no contraindications
for anticoagulation were on prophylaxis with warfarin 1mg daily.
No patients developed thrombocytopenia or thromboembolic
episodes. Thyroid function was monitored and remained normal
for euthyroid patients. Two patients who were on thyroxine had
to have the thyroxine dose increased during CDT treatment.
Fourteen patients experienced thalidomide related toxicity (grade
I neuropathy –sensory, grade II depressed level of consciousness
and grade II constipation). CDT was administered for up to 6
courses in responding. Fourteen patients (61%) had very good
and rapid response to treatment with >90% reduction of
paraprotein at a mean of 2.5 months. These patients completed
six courses and remained on thalidomide maintenance 100mg
with sustained response at median time of 5 months follow-up
(range 3 to12 months). Three patients (13%) had minimal
response with at least 25% reduction of paraprotein, 5 patients
(22%) showed no change with stable disease and one patient died
from disease progression. All patients with severe anaemia
became transfusion independent following response. Six patients
with severe renal impairment received treatment with no
increased toxicity and 3 showed marked improvement in renal
function. Two of the good responders have successfully
undergone a second stem cell autograft.
Conclusion: CDT is a well-tolerated oral regimen, which has high
activity in relapsed/refractory myeloma. These preliminary
results are encouraging considering the prognosis and therapeutic
options available for this group of patients. Treatment related
toxicity was low and a significant proportion can be salvaged.
Longer follow-up and more patients are required to determine the
true value of this approach.
335
Thalidomide in combination with Dexametasone and
Cyclophosphamide for relapsed/refractory multiple
myeloma
Caravita T., Siniscalchi A., Postorino M, Franchi A., Masi M.
and Amadori S.
Hematology, University Tor Vergata, St. Eugenio Hospital, Rome,
Italy.
INTRODUCTION: The antimyeloma effect of thalidomide
(Thal) alone has been demonstrated in several clinical trials.
Recent data indicate that Thal can increase the therapeutic effect
of chemotherapy and might be able to overcome drug resistance.
Response rates of 25% with Thal used as a single agent, and up to
75%, when used in combination with other agents, have been
observed. The optimal schedule, dosage and association with
other drugs is still not established. MATERIAL AND
METHODS: Between October 2001 and December 2002 twelve
patients (pts) (10 M/ 2 F) with relapsed/refractory MM were
enrolled in an open-label trial of oral low dose Thal (100-200
mg/day) plus Dex (40 mg, day 1-4, every month) and
cyclophosphamide (500 mg iv/week). Main pre-treatment
characteristics were the following: median age 66 years (range
54-74); median B2M 3.3 mg/L (range 1.2-14.2); median bone
marrow plasma cell infiltration 32.5% (range 4-80). Median time
from MM diagnosis to treatment was 60 months (range 6-132).
All pts were heavily pre-treated. In particular, 9 pts received a
median of 3 pre-treatment chemotherapy regimens (range 1-5)
and 3 underwent autologous stem cell transplantation. In addition
11 pts showed disease progression during previous treatment with
Thal alone or combined with Dex. The EBMT/IBMTR/ABMTR
criteria were used for definition of response. RESULTS: Adverse
effects were moderate (grade or=2 were observed, while 2 pts
experienced neutropenia requiring supportive treatment with G-
CSF. Other side effects included grade 50% M-component reduction; while 3 (25%) showed disease
progression. At present 8 pts are alive and maintaining the
response for 1-8 months; while 4 pts died due to disease
progression, including one progressed after a 5 months response.
CONCLUSION: These results show that the Thal plus Dex and
cyclophosphamide combination is active and feasible in heavily
pre-treated multiple myeloma pts, including those relapsing after
Thal+Dex therapy. Further studies and a longer follow-up are
warranted to evaluate the duration of favorable responses, the
effect on survival and possible long-term side effects.
336
Salvage treatment with thalidomide, dexametasone and
zolendronate in advanced multiple myeloma: the
pattern and the outcome of relapsed/refractory disease.
Pasquale Niscola, Laura Scaramucci, *Alessandro
Andriani, Marco Morucci, Velia Bongarzoni, Roberta
Ciafrino, Cinzia De Gregoris, Vincenzo Tini and Marco
Montanaro.
Haematology Unit, ASL Viterbo, Viterbo (Italy), *Hematology Unit,
San Giacomo Hospital, Rome (Italy).
Thalidomide (thal) plus dexamethasome (dex) is an effectiveproven
salvage treatment in MM, allowing to obtain a response in
an about one third of pre-treated patients. Zolendronate is an
active agent in bone disease and it’s maybe provided of direct
anti-myeloma effects. This combined therapy represent the most
innovative current approach in the management of advanced
MM.
However, the illness relapse is therefore unavoidable and the
patients, having few therapeutic options, can only benefit of
supportive measures.
The pattern and the outcome of relapsed/refractory disease in 21
consecutive patients (8 M / 13 F, median age 74 yrs) with pretreated
advanced MM receiving a salvage treatment with thal, dex
and zolendronate, are reported. Thal was given at a median dose
150 (100-400) mg/day, dex and zolendronate were respectively
given at the dose of 40 mg/day I.V or P.O. for 4 days and of 4 mg
as single I.V. infusion both every 4 weeks. Eight out of 21 (38%)
showed a stable disease,5 (24%) progressed and 8 (38 %)
responded. Out of the 8 responders, one deceased without relapse
(congestive hearth failure) and 7 relapsed. Median duration of
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