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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2272-2272
CORRESPONDENCE
To the editor:
Deep-vein thrombosis in patients with multiple myeloma
receiving first-line thalidomide-dexamethasone therapy
Thalidomide has emerged as an active agent for the management of
advanced multiple myeloma (MM) and is currently under investigation also in patients with newly diagnosed disease.1 It is
relatively well tolerated; more common side effects include
constipation, sedation, skin rash, fatigue, and peripheral
neuropathy.2,3 Recently, an increase in the frequency of
deep-vein thrombosis (DVT) from 1% with thalidomide
alone2 to the range of 21% to 28% with thalidomide plus
chemotherapy was reported by several groups,4-6 more
frequently in association with doxorubicin-contaning regimens.7 We report here on an unexpectedly high
incidence of DVT in patients with newly diagnosed, symptomatic MM who
received first-line therapy with thalidomide-dexamethasone. By study
design, both drugs were administered for 4 months in an attempt to
reduce tumor cell mass before collection of peripheral blood stem cells to support 2 subsequent autotransplants. The starting dose of thalidomide was 100 mg/d, with a subsequent increase to 200 mg/d after
14 days; the monthly dose of dexamethasone was 40 mg/d for 4 days, with
cycles repeated on days 9 to 12 and 17 to 20 on the first and the third
month of therapy. At the present time, 19 patients entered this phase
II trial and received at least 2 months of therapy. Of these 19 patients, 5 (26%) had symptomatic DVT, of whom 1 had associated
nonfatal pulmonary embolism. DVT was documented by doppler
ultrasonography and developed in the lower extremities (popliteal vein:
3 patients; calf veins: 2 patients). Thrombosis occurred during the
first month of therapy in 2 patients, the second month in 1 patient,
the third month in 1 patient, and at the end of the fourth month of
therapy in the last patient. Baseline laboratory evaluation for
inherited risk factors for thrombosis including antithrombin III
deficiency, protein C and protein S deficiencies, resistance to
activated protein C, lupus anticoagulant and antiphospholipid
antibodies, and prothrombin gene abnormalities (G20210A)was performed
in all patients and excluded primary hypercoagulable states. Additional
risk factors for thrombosis included hormonal therapy in a single
patient. Anticoagulation therapy consisting of low-molecular-weight
heparin with or without warfarin was promptly started after
the diagnosis of DVT. There were 3 patients who safely continued
thalidomide-dexamethasone without evidence of progression of DVT;
thalidomide was stopped in the other patients, 1 with associated
pulmonary embolism and 1 by study design before priming therapy with
high-dose cyclophosphamide. In addition to recent reports on the use of
thalidomide administered in combination with multiagent chemotherapy
and dexamethasone,4-6 present data show an increased risk
of DVT also for patients with MM receiving first-line
thalidomide-dexamethasone. This observation was not reported in
previous studies with the same regimen, but different thalidomide and
dexamethasone dose intensities, as salvage therapy for patients with
advanced and refractory MM.7,8 Efforts aimed at
elucidating biologic mechanisms associated with thrombosis and
thalidomide-based therapy should continue. In the interim, careful
monitoring for DVT should be recommended for patients enrolled in
investigational clinical trials including thalidomide as part of
therapy for MM. In these patients prophylactic low-dose warfarin should
be considered in an attempt to reduce the risk for DVT.
Michele Cavo, Elena Zamagni, Claudia Cellini, Patrizia Tosi, Delia Cangini, Michela Cini, Lelia Valdrè, Gualtiero Palareti, Luciano Masini, Sante Tura, and Michele Baccarani
Correspondence: Michele Cavo, Institute of Hematology and
Medical Oncology "Seràgnoli," via Massarenti 9, 40138 Bologna, Italy; e-mail: mcavo{at}med.unibo.it.
Acknowledgments
Supported in part by Università di Bologna, Progetti di
Ricerca ex-60% (M.C.).
References
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2.
Singhal S, Mehta J, Desikan R, et al.
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Tosi P, Zamagni E, Cellini C, et al.
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Zangari M, Anaissie E, Barlogie B, et al.
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