Thalidomide therapy in adult patients with myelodysplastic syndrome

Abstract

The results recently published in Cancer by Moreno-Aspitia et al.1 concerning the unsatisfactory therapeutic effects of thalidomide in myelodysplastic syndromes (MDS) warrants some comments. This study was designed in 1998, the enrollment of patients closed in 2002, and the full paper published in 2006. During this very long time, at least 4, noncited, additional articles dealing with the same topic were published,2-5 reporting an overall response rate ranging from 16 to 56% in the intention-to-treat setting and from 31% up to 88% when considering only patients able to receive the drug for an adequate time (12–16 weeks). The high drop-out rate due to severe side-effects that occurred, likely correlated with the very high thalidomide doses employed in their study, certainly contributed to the quite different and disappointing results obtained by Moreno-Aspitia and coworkers. However, there are other possible reasons to explain such differences, first of all, the selection of patients. Moreno-Aspitia et al. enrolled not only anemic subjects but also patients with transfusion-dependent thrombocytopenia or marked neutropenia. It is now clear by other studies that the large majority of responses in MDS patients who are receiving thalidomide are erythroid in nature and that patients with “advanced disease” (criterion for inclusion in that trial) are significantly less prone to respond. This is particularly true if these patients have a long history of disease, as suggested by the very short median survival (only 17 months!) observed even in the “favourable group”, which included patients with an International Prognostic Scoring System (IPSS) score of 0–1, who usually have an expected survival of 3–5 years. In addition, the elevated mean age of patients and the high proportion of MDS with blast excess reported also represent potential predictive factors of poor response to thalidomide. Indeed, in our updated, still unpublished experience, which currently includes 67 anemic, transfusion-dependent MDS patients treated with thalidomide, patients aged younger than 70 years, with anemia as single cytopenia, no blast excess, and a short history of disease had the highest chance (62.5%) to obtain an interruption of their red cell transfusional support after a treatment with individualized (but no more than 200 mg/day) doses of thalidomide. In particular, we observed significant (and sometimes long-lasting) erythroid responses even in patients who did not tolerate “conventional” (100–200 mg/day) doses of thalidomide, but who were able to assume 50 mg/day or even on alternate days for at least 3 months. Thus, in my opinion, thalidomide remains a possible therapeutic option for selected MDS patients, if appropriately used and managed. Pellegrino Musto MD*, * Unit of Hematology and Stem Cell Transplantation Centro di Riferimento Oncologico della Basilicata (C.R.O.B.) Rionero in Vulture (PZ) Italy.