Treatment of Lower Risk MDS with Del 5q by Lenalidomide, with or without G-CSF: Current Results of the French Patient Named Program (ATU)

Background: LEN is very effective for the anemia of lower risk MDS with del 5q. A patient named program was launched by the French health agency (AFSSAPS) to use LEN in low and int 1 risk MDS with del 5q and transfusion dependence (> 2 RBC units/2 months).

Methods: Patients received 10 mg of LEN/day, 3 weeks on, 1 week off. Hematological response (IWG 2006) was assessed after 8, 16 and 32 weeks of treatment. G-CSF use was recommended in case of grade 3 neutropenia, in order to avoid dose reduction, especially during the first 16 weeks of treatment.

Results: 71 pts from 35 centers were evaluable for response as of Aug 1st, 2008. Median age was 75 [range 43–93], 68% females, median interval from diagnosis to LEN treatment 28.6 months (range 1–235). At inclusion, 32 pts had del 5q syndrome, 10 RA, 13 RARS, 2 RCMD-RS and 14 RAEB-1. IPSS was low in 43% and int-1 in 57%. Del 5q was isolated, with 1 additional and > 1 additional abn in 76%, 15% and 9% pts respectively. 23 pts were untreated, while 48 had previously received EPO. Median transfusion requirement was 4 units/2 months. 50/71 (69%) pts achieved erythroid response (IWG 2006), of whom 48 (67%) achieved transfusion independence (TI). Median time to TI was 12 weeks (range 8 – 32). TI was achieved in 76%, 62%, 68%, 70% and 50% pts with IPSS low, IPSS int 1, isolated del 5q, del 5q+1abn, del5q + >1abn, resp, and 70% and 65% of EPO pretreated and EPO naive pts (p=NS). Grade III-IV neutropenia and thrombocytopenia were seen in 86% and 26% pts resp, leading to transient discontinuation followed by reduction of LEN dosing in 55%pts. Of the 19 pts who received GCSF, 3 (16%) required transient LEN discontinuation due to neutropenia compared to 15 (28%) of the 52 who did not receive GCSF (p=0.3). Apart from neutropenia and thrombocytopenia, grade III–IV side effects were Lyell’s syndrome (n=1), deep venous thrombosis (n=3) Quincke’s oedema (n=1), No patient died from sepsis due to neutropenia or bleeding due to thrombocytopenia. With a still short median follow up on treatment (28 weeks), no relapse had occurred. 1 pt (RAEB 1 with 7% of blasts, isolated del 5q and IPSS INT-1 at inclusion who had achieved TI) progressed to AML at week 48.

Conclusion: Our results confirm on a very multicenter basis the efficacy of LEN on the anemia of lower risk MDS with del 5q,. The use of G-CSF during the early treatment phase may somewhat reduce the proportion of early LEN discontinuation due to neutropenia.