Lenalidomide reexposure After Short Interruption In Del(5q) MDS Patients at Relapse of Transfusion Dependence

Lenalidomide is effective in myelodysplastic syndroms (MDS) in patients with del(5q) chromosomal abnormality (List et al 2006). However, relapse of transfusion dependence occurs consistently and therapeutic measures at that moment are scarce. We report on our experience to achieve a second remission of transfusion dependence using lenalidomide after a variable period of lenalidomide treatment interruption.

5 patients with a del(5q) chromosomal abnormality (low- and intermediate-1-risk MDS according to IPSS) were treated within clinical trials, all transfusion-dependent with a median age of 67 years and with female prevalence. Mean MDS duration before start of lenalidomide therapy was 4.2 years. Patients were treated with doses of oral lenalidomide ranging from 5 mg every other day to 10 mg for 28 days of every 28 days cycle. All patients had a response to the initial lenalidomide treatment and achieved transfusion independence. All 5 patients relapsed and became red cell transfusion dependent, again. Median time to relapse was 24.2 months (13-55 months).The therapy was stopped and after a therapy-free interval of 7.2 months (2-13 months) we resumed lenalidomide therapy. The patients were treated with the initial lenalidomide dose.

3 of 5 patients (60%) became transfusion independent, again. The median increase in hemoglobin from baseline to the maximum hemoglobin achieved was 4.4 g/dl. Patients are followed up and all of them are currently in ongoing transfusion independence with a median time of 16.3 months (11, 15, 23 months, respectively). The other two patients stayed transfusion dependent and lenalidomide was interrupted after 3 and 4 months, respectively. Both later progressed to higher MDS subtypes or acute myeloid leukemia. Responses seemed to be independent on age, time to relapse, interval to retreatment or doses of lenalidomide.

In low/int-1 IPSS del(5q) patients relapsing with red cell transfusion dependence during lenalidomide treatment, current algorithms recommend discontinuation of the drug. Our results suggest efficacy of lenalidomide in a significant portion of the patients when they are rechallenged with a standard dose after a therapy-free interval of 2 to 6 months. Second remissions might be as long lasting as, or exceeding, the initial one. We are unable to define predictive factors for second responses. Lack of further response may be an ominous prognostic sign and, in our experience, heralded progression to higher risk MDS subtypes or acute myeloid leukemia after a short time.

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