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Thalidomide and Combination Chemotherapy Linked to Deep Vein Thrombosis in Multiple Myeloma Patients

Myeloma patients treated with multi-agent chemotherapy and thalidomide are at risk of thrombotic complications, particularly at early stages of treatment, say researchers.

Thalidomide is an effective therapy for refractory multiple myeloma. Originally introduced as a single-agent therapy, patients receiving thalidomide treatment showed no significant cardiovascular toxicity. When thalidomide was later combined with multi-agent chemotherapy, however, DVT incidence doubled over that previously observed.

Maurizio Zangari, MD, associate professor of medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States, and colleagues performed a retrospective study to determine the incidence of thrombogenic complications occurring in myeloma patients treated with thalidomide either as a single or combined agent.

The researchers evaluated data associated with 535 patients treated with thalidomide with dexamethasone only or in combination with cytotoxic chemotherapy, including VAD (vincristine/doxorubicin/dexamethasone), CAD (cyclophosphamide/doxorubicin/dexamethasone), DCEP (dexamethasone/cyclophosphamide/etoposide/cisplatin), or DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide).

A total of 82 patients developed deep vein thrombosis (DVT). The majority of DVTs occurred early in the course of treatment, with approximately 88% of cases developing within the first 6 months.

The combination of thalidomide and chemotherapy with adriamycin was the strongest predictor for DVT (OR, 4.3; P = 0.001). Other independent predictors of DVT included new diagnosis (OR, 2.5; P = 0.001) and chromosome 11 abnormality (OR, 1.8; P = 0.048).

Surprisingly, the development of DVT did not adversely affect survival when examined as a time-dependent variable and when adjusted for standard risk factors (hazard ratio, 0.8; P = 0.162). None of the occurring DVT cases were fatal.

Researchers note that the acquired hypercoagulable status triggered by the combination of thalidomide with specific drugs in multiple myeloma patients is also documented in patients with renal-cell carcinomas and prostate cancer.

"To fully evaluate the potential combined therapeutic effect of chemotherapy and thalidomide, effective prophylactic anticoagulation should be tested in controlled trials," the researchers conclude.
Clin Lymphoma 2003 Jun;4:1:32-5. "Thalidomide and deep vein thrombosis in multiple myeloma: risk factors and effect on survival"

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