Single agent thalidomide in patients with relapsed or refractory acute myeloid leukaemia

Thalidomide is a putative anti‐angiogenesis agent that has significant anti‐tumour activity in haematological malignancies with increased bone marrow angiogenesis, including multiple myeloma (MM) and myelodysplastic syndromes (MDS). Increased levels of the mitogen for angiogenesis, vascular endothelial growth factor (VEGF), correlate with worse survival in acute myeloid leukaemia (AML). A phase II trial of thalidomide was conducted in patients with relapsed‐ or refractory‐AML previously treated with cytarabine‐containing regimens. A total of 16 patients with refractory‐ or relapsed‐AML were treated with thalidomide 200–800 mg orally daily (median dose 400 mg daily) for a median of 27 d (range, 3–94 d). Overall, one patient (6%) achieved complete remission (CR) lasting for 36 months, and two patients had a transient reduction in marrow blasts from 8% and 7% to less than 5% in both cases. There was no correlation between reduction in levels of angiogenesis markers and response. Toxicities related to thalidomide were significant, and precluded dose escalation beyond 400 mg orally daily in most patients. Although there appears to be some evidence of biological activity, single agent thalidomide is not an optimal choice of therapy for salvaging patients with relapsed‐ or refractory‐AML. Thalidomide analogues with more potent immunomodulatory activities and more favourable toxicity profiles may offer more promise as anti‐AML therapy.