Discontinuation of Lenalidomide in Patients with Transfusion-Dependent Low- and Intermediate-1 Risk Myelodysplastic Syndromes with Del(5q): Sustained Remissions, but Not Cure.

Lenalidomide has high erythroid remitting activity in patients with del(5q) myelodysplastic syndrome (MDS). The actual recommendation is to continue drug administration until relapse of red blood cell transfusion dependence. We address the question whether it is safe and advisable to discontinue lenalidomide after achieving a hematologic and/or cytogenetic response

13 patients (8 female, 5 male) were treated with lenalidomide between December 2003 and January 2007. Median age was 69 years. All had low- or intermediate-1 risk MDS with del(5q) chromosomal abnormality. All patients were red blood cell (RBC) transfusion dependent. All patients started treatment with 5 or 10 mg lenalidomide for 28 out of 28 days or for 21 out of 28 days. Discontinuation of lenalidomide was usually due to patient's choice, and occurred after achievement of RBC transfusion independence. Lenalidomide administration duration ranged from 6 weeks to 24 months

Four patients had a total lenalidomide exposure of > 12 months (12, 15, 18 and 24 months), seven patients between 4 and 12 months and two patients had lenalidomide exposures of <4 months (3,5 and 1 month). Five patients achieved partial cytogenetic remission, and eight patients complete cytogenetic remission (CCR), i.e. disappearance of all del(5q) metaphases in conventional cytogenetics. Within the five patients with partial cytogenetic remission, both patients with very short lenalidomide treatment (1 and 3.5 months) achieved transfusion independence of 21 months duration. At relapse, one was progressing to RAEB-1. One patient who received lenalidomide for four months remained RBC transfusion independent for 12 months. At relapse, she resumed lenalidomide for 6 months and became transfusion independent again (16+ months). One patient received lenalidomide for eight months and remains transfusion independent after 26+ months with normalized and stable hemoglobin value. One patient received lenalidomide for 12 months and remains transfusion independent for 30+ months, but hemoglobin levels have fallen recently to 11 g/dL, indicating imminent relapse. Eight patients achieved complete cytogenetic remission: Two administered lenalidomide for 24 months, one for 18 months, three for 15 months, one for 12 months and one for 9 months. Duration of RBC transfusion independence in these patients was dependent on the length of lenalidomide administration after achievement of CCR: One patient stopped lenalidomide at the time of CCR. She remains transfusion independent after 18+ months, but del(5q) karyotype has reoccurred after 12 months. Three patients stopped lenalidomide two, four, and seven months after CCR. Transfusion-independence is ongoing at 34+, 36+ and 38+ months. In all patients del(5q) has reoccurred. Three patients discontinued after >12 months of CCR achievement. They are transfusion independent for 27+ months, 41+ months, and 66+ months. The latter patient had reoccurrence of one metaphase out of 20 with del(5q) after 60 months. Finally, one patient took lenalidomide only six months beyond CCR and remains in transfusion independence for 70+ months. However, this patient was trated with a fludarabine-containing regimen for follicular lymphoma 48 months ago

Discontinuation of lenalidomide seems to be feasible in patients with del(5q) MDS, preferably in those who achieve CCR. Best results regarding long-term transfusion independence and long-term complete cytogenetic remissions are seen in patients who continue lenalidomide for 12 months after CCR achievement.

Giagounidis:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Göhring:Celgene Corp.:. Schlegelberger:Celgene Corp.:. Kuendgen:Celgene: Honoraria. Platzbecker:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.