Low Doses of Thalidomide (Thal) in Low Risk MDS with Transfusion-Dependant Anemia: The GFM THAL-SMD-200 Trial.

Background: Thal has shown some efficacy in low risk MDS, but with dose-limiting toxicity requiring discontinuation in > 50% pts (

Methods: From Jan 2003 to Oct 2005, we performed a prospective study of low dose Thal in 87 MDS pts with transfusion-dependant anemia (THAL-SMD-200 trial). The first 59 pts received Thal at 200 mg/d, whereas the last 28 pts received 50 mg/d. Responses (IWG) were evaluated at week 12.

Results: 48 M and 39 F pts were included. Median age 73.6 years. IPSS Low 34 pts, INT-1 44 pts, INT-2 9 pts. Mean number of RBC units transfused within 2 months of inclusion 6 (2–16). Median ANC, plts, Hb were 1960/μl (0–24160), 164 000/μL (1 000–789 000) and 8,2 (5,1–14,7) resp. 14 (16%) patients had del 5q. Thirty two (37%) pts stopped Thal before week 12, 19 (32%) and 13 (46%) patients in the 200mg/d and the 50mg/d groups resp. Reasons for interruption were: important toxicity in 23 (72%) (mainly dizziness, fatigue, sleepiness), patient’s decision in 6 (19%), progression to AML in 3 (9%) and death in 1 (3%). 3 pts developed deep venous thrombosis in the 200mg/d group (none in the 50mg/d group). 55 patients completed 12 weeks of treatment, 22 of them (40%, ie 25% of pts included) had an erythroid response, including 12 major responses (HI-EM) and 10 minor responses (HI-Em). We observed 17 (43.5% of pts who completed 12 weeks, 28% of all pts) and 5 (29.4% of pts who completed 12 weeks, 18% of all pts) erythroid responses in the 200mg/d and the 50mg/d group respectively, not statistically different (p = 0,27). Erythroid response was seen in 15 (44%) patients with IPSS low, versus 6 (14%) in INT-1 and 1 (11%) in INT-2 resp (p = 0.005), whereas no other prognostic factor of response was found. No neutrophil or platelet response was seen.

Conclusion: Thal at 200mg/d improved erythropoiesis in 40% of the pts who reached week 12 (28% of included pts). Side effects leading to treatment interruption < week 12 occurred in 32% of pts, ie a similar efficacy and somewhat better tolerance than in our experience with higher doses. Most erythroid responses occurred in IPSS Low pts. On the other hand, Thal at 50mg/d gave a similar incidence of side effects as 200mg/d, with slightly lower but not statistically different erythroid response rate, and thus brought no obvious benefit over 200mg/d. Longer follow up of pts who continued Thal will be presented.