Lenalidomide (LEN) In Lower-Risk Myelodysplastic Syndromes (MDS) with Karyotypes Other Than Deletion 5q and Refractory to Erythropoiesis-Stimulating Agents (ESAs)

In lower-risk MDS, anemia is the main therapeutic challenge. ESAs can frequently correct anemia, but not all pts respond and median response duration to ESAs is only about 2 years. LEN yields RBC transfusion-independence (TI) in 65% of lower risk MDS with del(5q)] and about 25% of lower risk MDS without del 5q (Raza A, et al, Blood, 2008, 111, 1). However, in the last study, pretreatment with ESAs was not always documented, and the efficacy of LEN on anemia of non-del(5q) MDS refractory to ESAs remains unknown.

31 consecutive lower-risk non-del(5q) MDS with anemia refractory to ESAs were treated with LEN through a compassionate program. Pts wn@ere from 7 centers of the Groupe Francophone des Myélodysplasies. They had previously received an ESA during at least 12 weeks, including epoetin alfa (80,000 U qw, n= 17), epoetin beta (60,000 qw, n=3), darbepoetin (500 μg q2 w, n=11), and GCSF was added in 20 patients.

At inclusion in the program, median age was 69 (range 41–87), including RA (n=3), RAEB-1 (n=2), RARS (n=11), RCMD (n=12), and RCMD-RS (n=3). Karyotype was fav (n=27), int (n=2), and unfav (n=2). IPSS was low (n=15), int-1 (n=16). Median ESAs treatment duration was 3 months (3-36⁺). According to IWG 2006 criteria, 18 pts were primary resistant to ESAs while 13 relapsed after a 12 months median duration of erythroid response (range 3–36). At onset of LEN, median Hb level was 8.9 g/dl (range 6.3–9.9), median endogenous EPO level 172 UI/l (48-1092 UI/l). The starting doses of LEN were 5 (n=10) or 10 mg (n=21), daily (n=26) or daily × 3 wks q28d cycle (n=5). 20 pts also received ESAs including EPO alone (n=6) and EPO+GCSF (n=14). Deep vein thrombosis (DVT) prophylaxis was made in 22 pts (71%) with aspirin (n=20), heparin (n=1) or warfarin (n=1). With a median follow-up of 16 months (range 3–27), 13 (42%) pts obtained an erythroid response (IWG 2006 criteria). All responses occurred within the first 3 months of treatment. 4 of the responders (31%) relapsed at 4, 9, 15, and 16 months whereas 9 (69%) were still responding after 3⁺ to 24⁺ months. Median response duration was 12 months. Of the 24 RBC-TD patients, 10 (42 %) achieved RBC-TI of 12 months median duration (range 3⁺-22⁺). The most common drug-related grade 3/4 adverse events were neutropenia (n=6, 19%) and thrombocytopenia (n=6, 19%). No pt developed DVT. One pt with RCMD and complex karyotype developed AML and died at 3.1 months from treatment onset, 2 additional pts who resisted to LEN died 5 and 6 months after LEN interruption. According to IWG 2006 criteria, the proportion of erythroid responses was significantly lower in the 8 patients who had developed neutropenia or thrombocytopenia: 1/8 vs 12/23, p = 0.038. Among the 24 RBC-TD patients, the proportion of RBC-TI was significantly lower in the 8 patients who had developed neutropenia or thrombocytopenia: 1/8 vs 9/16, p = 0.05. Median RBC-TI duration was significantly lower in the 8 patients who had developed neutropenia or thrombocytopenia: 0 vs 9 months, p=0.05. Other factors such as age, sex, WHO classification, time between diagnosis and treatment, response to ESAs, interval between ESAs and REV, WBC count, hemoglobin level, platelet count, LEN dose, combination to ESAs, did not significantly influence response to LEN, and RBC-TI duration.

In this cohort of lower-risk non-del(5q) MDS refractory to ESAs LEN yielded RBC transfusion independence in more than 40% of the pts and was well-tolerated. Treatment-induced cytopenia was associated with fewer erythroid responses and shorter response duration.

No relevant conflicts of interest to declare.