Haematologica 2003 - Supplements

cases), soft tissue plasmacytoma (2 cases) and mediastinal
lymphadenopathy (1 case), without increase of serum and/or
urine monoclonal protein.
Conclusion: Our data indicate that after treatment with TBR in
some patients with reduction of monoclonal protein the bone
marrow plasmacytosis may persist. Furthermore some patients with
both monoclonal protein and bone marrow response may progress
in the bone marrow with or without extramedullary involvement
but without a concomitant increase of paraprotein. If our data are
confirmed, they may have practical implications for assessment of
response and follow up of patients treated with TBR.
332
Preliminary Efficacy of a Phase I/II trial of Oblimersen
Sodium (G3139, bcl-2 antisense oligonuceleotide)
combined with Dexamethasone and Thalidomide in
Patients with Relapsed Multiple Myeloma
Ashraf Badros, Robert Fenton, Aaron Rapoport, Naoko
Takebe, Stanley Frankel, Jerome B.Zeldis, Sabrina Natt,
Bashi Ratterree, Judith Karp, James Zwiebel
Greenebaum Cancer Center, University of Maryland at Baltimore;
National Cancer Institute, Bethesda, Maryland; Genta Inc.,
Berkeley Heights, NJ
Bcl-2 plays a major role in drug resistance in MM. In an attempt
to overcome drug resistance and increase remission rate in
relapsed/refractory MM patients, we administered G3139 to
down regulate Bcl-2 [3-7 mg/kg/ivci days 1-7 repeated every 3
weeks] and to sensitize drug-resistant MM cells to subsequent
administration of dexamethasone (40 mg po day 4-7 of each week
of G3139) and thalidomide (100 mg po increasing to 400 as
tolerated). After 3 cycles, responding patients (pts) proceeded to
a maintenance phase with G3139 repeated every 5 weeks with
dexamethasone at 20 mg po days 4-7 of each infusion;
thalidomide is continued at the tolerated dose for up to 1 year.
Bone marrow aspirates were performed on days 1, 4, 28 and at 3
months. Plasma cells were selected from these samples by CD138
beads and evaluated for Bcl-2 expression and apoptotic signaling.
Nine patients have been treated to date. The median age was 64
years (range 51-74). Patients had a median of 4 prior therapeutic
regimens (range 2-4), including auto-transplants in 7 and
thalidomide in 5. Five patients had a complex karyotype
including chromosome 13 deletions.
Three pts had a creatinine > 2 mg/dl at baseline; 4 pts had
platelets < 100,000/ul secondary to plasmacytosis.
The initial 3 pts received a G3139 dose of 5 mg/kg/day. Three
pts with renal insufficiency received 3 mg/kg/day of G3139. All
other patients are treated at 7 mg/kg/day for each 7-day cycle.
Five patients have completed induction therapy: 4 had major
responses, including 1 CR and 3 PR; 1 pt had stable disease.
Evaluation of the laboratory correlates in the plasma cell
population is ongoing.
Toxicities associated with G3139 infusion included mild
thrombocytopenia in 3 pts (35,000-80,0000/uL) that did not require
transfusional suppport, grade 2 fatigue (n=2) and fever (n=2).
Creatinine rose in patients with underlying renal insufficiency.
Toxicities associated with thalidomide included neuropathy (grade
1, n=4), constipation (n=3) and fainting (n=1). Two patients
required reduction of thalidomide dose due to toxicity.
We have established that G3139 at 7 mg/kg/day is well tolerated
in combination with thalidomide and dexamethasone in MM
patients with serum creatinine less than 2.0 mg/dl. The early
responses observed in previously refractory patients is
encouraging and may indicate that G3139 may overcome
resistance to dexamethasone and thalidomide.
333
Low dose thalidomide plus dexamethasone for
relapsed/refractory multiple myeloma: a single center
experience.
T.Caravita, A.Siniscalchi, S.Santinelli, M.Postorino,
A.Franchi, M.Masi and S.Amadori
Hematology, University Tor Vergata, St. Eugenio Hospital, Rome,
Italy.
Thalidomide (Thal) is a promising new drug for
relapsed/refractory multiple myeloma (MM). Literature data
show prolonged survival in patients (pts) treated with Thal, but
the optimal schedule, dosage and association with other drugs is
under investigation. The association of Thal with dexamethasone
(Dex) seems to be highly effective in advanced MM, including
pts previously resistant to Dex and chemotherapy. Between
January 2001 and January 2003 thirty pts (8 females and 22
males) with relapsed/refractory MM were enrolled in an open
label trial of oral dose Thal (100-200 mg/day) plus Dex (40 mg,
days 1-4, every month). The main pre-Thal treatment
characteristic were the following: median age 64 years (range 54-
80); median B2M 3.3 mg/L (range 1.06-14.2); median bone
marrow plasma cell infiltration 30% (range 4-90). Eight pts were
previously treated with autologous stem cell transplantation,
while 22 pts had received more than two chemotherapy regimens.
Median time from MM diagnosis to Thal treatment was 30
months (range 5-124). A total of 28 pts were evaluable with a
median follow up of 6 months (range 1-20), while 2 pts were not
evaluable because of early withdrawal (50% M-component reduction, while 6 pts had disease
progression. Median time to response was 2 months (1-3).
Projected EFS and OS at eleven months were 28% and 63%,
respectively. As to side effects, treatment was discontinued in 6
pts due to neurotoxicity (4 cases) and deep venous thrombosis (2
cases). Otherwise, low dose Thal plus Dex was well tolerated and
only minor toxicities were recorded in six pts (mild somnolence
and constipation). Data analysis did not show any correlation
between pre-treatment characteristics and treatment response. In
conclusion, our results confirm that low dose Thal plus Dex is
highly effective and feasible in pts with relapsed/refractory MM.
Further studies and a longer follow-up are warranted to evaluate
the duration of the favorable responses, the effect on survival and
possible long-term side effects.
334
Salvage therapy with Cyclophosphamide,
Dexamethasone and Thalidomide (CDT) is a welltolerated
and effective regimen in advanced
relapsed/refractory myeloma
C. Kyriakou MD, S. D’Sa MD, R. Fox, J. Hanslip MD, K.
Peggs MD, KL Yong MD, PhD.
Department of Haematology, University College London
The combination of Thalidomide and Dexamethasone produces a
response rate of 30% to 40% in refractory myeloma and 80% to
90% in de novo disease. We have carried out a pilot study to
assess the efficacy and tolerability of the combination of
cyclophosphamide, dexamethasone and thalidomide (CDT) in
myeloma patients who have previously failed multiple treatment
lines.
Patients and Methods: Twenty-three patients (16 Males, 8
Females, mean age 55 years, range 37 to 70 years) were treated
with CDT between March 2002 and February 2003. The average
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