Thalidomide for the Treatment of Low Risk Myelodysplasia.
Authors: Bouscary D. , Quarre M. C. , Vassilief D. , Rouzy O. Beyne , Aouba A. , Berthou C. , Gardembas C. , Sanhes L. , Guerci A. , Mahe B. , Stamatoullas A. , Bauduer F. , Sotto J. J. , Legros L. , Vaultier S. , Fenaux P. , Dreyfus F. 
Published: October 2019

Abstract
We conducted a phase II trial of thalidomide in patients with low risk MDS issued from the GFM. 82 patients were included from january 2003 to june 2004: 38 RA, 19 RARS, 21 RAEB<10% blasts and 4 patients with undetermined MDS. The IPSS was Low in 21, INT-1 in 44, INT-2 in 7 and undetermined in 10 patients. Thalidomide was given at bedtime at 200mg/day for 12 weeks. The response was evaluated at week 12, according to the B Cheson criterias. Thalidomide was decreased to 100mg/day if side effects. In the absence of response at week 12, thalidomide was increased to 300mg/day for 8 weeks (up to week 20) and eventually to 400mg/day for 8 weeks more (up to week 28). The inclusion criteria was A = packed red blood cell transfusion requirement (PRBCR) in 67% of patients (55/82), B = neutropenia <1000/μl in 9% (8/82), C = thrombocytpopenia < 5000/μl in 35% of patients (29/82). 72 patients can be analyzed at week 12 (RA = 35, RARS = 15, RAEB = 20). The inclusion criteria for these patients was: A = 50/72, B = 8/72 and C = 28/72. 57% of RA (20/35), 93% of RARS (14/15) and 70% of RAEB (14/20) were included for criterai A (PRBCR). 47 ou of these 72 patients (65%) attained week 12, 15 had to stop at week 4 and 10 at week 8 because of side effects in 20, 2 retractions, 2 transformations and one early death unrelated to thalidomide. No hematological response was observed in these patients. At week 12, 14 patients stopped because of side effects (4 at 200mg and 10 at 100mg) and only one had a response: minor erythroid response (mER) and major response on neutrophils (MRN). 33 patients could continue above week 12. Among these, we observed 6 major erythroid response (MER) and 8 mER, 1 mEN, 2 major response on platelets (MRP) and 1 minor reponse on platelets (mRP). In an intention to treat analysis, 28% (14/50) of patients included for criteria A had an erythroid response. According to the FAB subtype, the 6 MER were: RA 4, RARS 1, RAEB 1 and responses were observed at 50mg in 1 patient, 100mg in 4, and 200mg in 1. All these patients had normal cytogenetic. The 8mER were obtained in 4 RA, 2 RARS, 1 RAEB and 1 patient with undetermined MDS, 3 at 100mg and 5 at 200mg, normal caryotype in 3, del 20q in 1, del 5q or monosomy 5 in 3, Unknown in 1. 28 patients are available for analysis at week 20. The hematological response are: MER = 5, mER = 3, mRP = 1. The MER is maintained in 5/6 of patients who were already in MER at week 12. The preliminary results of this study are: 1/ thalidomide is effective to improve erythropoiesis (28% of response) 2/ there is a very low response rate on neutrophils and platelets 3/ responses can be observed at 100 mg or even at 50mg/day 4/ patients who respond are essentially those with RA.
We suggest that thalidomide should be used at 50 or 100mg/day only in patients with a diagnosis of RA and who need red blood cells transfusions.