Haematologica 2003 - Supplements

We had 3 cases of severe thrombocytopenia not related to the
multiple myeloma and cleared up after discontinuation of
therapy.
Case 1: A 51- year- old female presented with stage I A IgGk
multiple myeloma in 1991; she achieved a complete remission
after a double autologous stem cells transplantation in 1998. She
relapsed in 1999. She was begun on thalidomide (100 mg/die) in
January 2001. Her paraprotein decrease from 1500 mg/dl to 900
mg/dl, the bone marrow plasmocytosis decreased to 15%. The
therapy was well tolerated, she had moderate constipation as a
secondary effect. In August 2002 she developed
thrombocytopenia (24.000/cc). The bone marrow aspiration
showed few marrow cells and 5% plasmocytosis . Her platelet
count reached a normal value after discontinuation of
thalidomide.
Case 2: a 66-year-old male presented with stage III A IgGk
multiple myeloma in 1999, refractory to different lines of
chemotherapy; he was given Thalidomide (100 mg/die) and
prednisone in May 2002. His paraprotein decreased from 7700
mg/dl to 1290 mg/dl and he achieved a better quality of life. He
developed thrombocytopenia in February 2003; plt= 2000/cc.
Case 3: a 75-year-old male presented with stage III A IgGk
multiple myeloma in 1999 refractory to standard chemotherapy;
he was begun on thalidomide (100 mg/die) in November 2001.
His paraprotein decreased from 8530 mg/dl to 3700 mg/dl.
Because of lethargy and neutropenia, as an adverse side effect the
thalidomide was reduced to 50 mg/die. In February 2003 he
developed thrombocytopenia (plt 5000/cc). The platelets count
increased (75.000/cc) after thalidomide discontinuation and
commencement of low doses of prednisone therapy .
In all patients the bone marrow aspiration showed few marrow
cells especially megacaryocytes and 10-20% plasmocytosis.
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TOLERANCE TO LONG-TERM THALIDOMIDE
THERAPY FOR PATIENTS WITH ADVANCED AND
REFRACTORY MULTIPLE MYELOMA
Claudia Cellini, Patrizia Tosi, Elena Zamagni, Delia
Cangini, Paola Tacchetti, Sante Tura, Michele Baccarani,
Michele Cavo
Institute of Hematology and Medical Oncology "Seràgnoli",
University of Bologna, Italy
Thalidomide is remarkably active in advanced relapsed and
refractory multiple myeloma (MM), so that its use has been
recently proposed either in newly diagnosed patients or as
maintenance treatment after conventional or high-dose therapy.
This latter therapeutic approach has risen the concern of side
effects of long-term therapy with this drug. In order to
investigate this issue we analyzed the outcome of 32 patients
(26M, 6F, median age = 61.5 yrs) who received salvage therapy
with thalidomide ± dexamethasone for longer than 12 months
(median 15 months, range 12 to 35 months) at our Center. All the
patients had achieved at least a minor response (> 25% decrease
in serum or urine M component) upon treatment with thalidomide
alone (200mg/day, n= 14) or thalidomide (200mg/day) and
dexamethasone (40mg/day for 4 days every 4 weeks) (n=18).
Thalidomide was initially well tolerated in all these patients;
grade II constipation was present in 34% of them but it was well
managed with supportive measures, lethargy was detected in a
minority (15%) of the patients. Neurotoxicity was the most
troublesome and frequent toxic effect that was observed, the
incidence averaging 69%. Among these 22 patients symptoms
included paresthesias, tremor and dizziness. Neurotoxicity was
grade 1 in 8 patients (36%); grade 2 in 9 patients (41%), thus
determining thalidomide dose reduction to 100mg/day; and grade
3 in 5 patients (13%) who had subsequently to interrupt therapy
despite their response. In these latter patients electromyographic
study revealed mixed sensorimotor peripheral neuropathy. The
incidence of neurotoxicity was comparable in patients receiving
either thalidomide alone or thalidomide + dexamethasone. These
results suggest that long-term thalidomide therapy in MM may be
hampered by the remarkable neurotoxicity of the drug, that
undergoes only minimal regression after treatment withdrawal.
Studies addressing the issue of the role of thalidomide as
maintenance therapy for MM are currently underway. In the
interim, alternative dosages and schedules of treatment with
thalidomide should be investigated.
361
Clinical and electrophysiological evaluation of
neuropathies developed during Thalidomide treatment
for Multiple Myeloma
T.Caravita°, F.Arciprete*, A.Siniscalchi°, S.Santinelli°,
M.Postorino°, A.Franchi°, C.Iani* and S.Amadori°
°Hematology, University “Tor Vergata”, Rome, Italy, and
*Neurology, University “Tor Vergata”, Rome, Italy
Thalidomide is a glutamic acid derivative with anti-angiogenic
and immunomodulating properties, that has recently proven
effective as a single agent in relapsed/refractory multiple
myeloma (MM). Furthermore, low dose thalidomide (Thal) and
dexamethasone (Dex) combination is effective in at least 50% of
pts resistant to chemotherapy. Peripheral neuropathy, mainly
axonal and sensory, has emerged as a principal dose-limiting side
effect of long-term Thal treatment. In order to further evaluate
drug-induced neurotoxicity we performed a prospective study
based on clinical and elettrodiagnostic follow-up of MM pts
treated with Thal. Twenty-eight relapsed/refractory pts (20 men
and 8 women), median age 64 years (range 54-80) were enrolled
in an open-label trial of oral low-dose thalidomide (100-200 mg
day) plus dexamethasone (40 mg, day 1-4, every month), and
underwent neurologic examination and nerve conduction study
(NCS) at time 0 (before treatment) and every three months during
therapy. Neurologic examination included grading of symptoms,
signs and NCS according to the total neuropathy score (TNS).
NCS also comprised recording of sensory nerve potentials
(SNAPs) and conduction velocity (CV) from median, radial and
sural nerves, and motor nerve action potentials (MNAPs), CV
and F waves from median, ulnar, tibial and peroneal nerves.
Before treatment three patients showed signs of axonal
demielinating neuropathy, and one patient a pure axonal
neuropathy. None of the 28 and 11 pts evaluated at 3 and 6
months, respectively, showed clinical or electrophysiological
changes. Six pts underwent the nine-month and 3 pts the twelvemonth
control; all of them showed new mild sensory neuropathy
or aggravation of pre-existing alterations, requiring Thal
discontinuation in 2 cases. Only one patient performed a control
at 15 and 18 months, showing a mild worsening that did not
require therapy withdrawal. These preliminary results suggest
that drug-induced neuropathy represent a complication of lowdose
Thal plus Dex treatment in MM pts. Further studies are
warranted to better evaluate long-term neurotoxicity of this
association.
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