Lenalidomide after Allogeneic Stem Cell Transplantation in Multiple Myeloma.

Background: Lenalidomide is an immunmodulatory drug, orally administered once daily, which is effective in relapsed multiple myeloma (MM). Here, we evaluated the efficacy and toxicity of lenalidomide in 16 MM patients with relapsed disease after allogeneic stem cell transplantation (allo-SCT).

Methods: Median age was 57 (range 37–68) years. The series included 5 females and 11 males. Prior to allo-SCT, all patients were heavily pretreated with multiple lines of chemotherapy, including high dose therapy with autologous stem cell support. Also, prior to lenalidomide treatment, other salvage therapies included donor lymphocyte infusions (DLI) in 93% of cases, thalidomide in 63%, and bortezomib in 88%. NCI-criteria were used to define toxicity. Lenalidomide was given 25 mg orally once daily on day 1–21 every 28 days. No prophylactic anticoagulation was used.

Results: The overall median number of completed cycles was 5 (range 1–10). Very good partial response (VGPR) was achieved in 13%, partial remission (PR) in 53%, and stable disease (SD) in 27% of the patients. During the follow up period, disease progression was observed in 50% of cases, and death in one patient. The median progression-free survival was 8 months, while the median overall survival was not yet reached. Hematotoxicity was the primarily and major encountered side effect (leukopenia: 6% grade 4, 19% grade 3, 19% grade 2, 38% grade 1; thrombopenia: 19% grade 3, 19% grade 2, 31% grade 1). This myelotoxicity led to dose reduction (usually 10 mg) in 44% of the patients. Infectious complications were observed in 25%. Non-hematological toxicity was also seen in 75% of cases (56% grade 1, 19% grade 2), consisting of cramps in the leg, constipation, symptomatic fatigue, nausea and progressing polyneuropathy (n=1). Thrombembolic complications (cerebral infarction) were observed only in one patient, who was receiving concomitant corticosteroid treatment for acute graft-versus-host disease (GvHD), but neurological symptoms resolved completely. GvHD of the skin under lenalidomide treatment was seen in 25% of cases (one grade 2, and 3 grades 1), with one case occurring shortly after an additional DLI.

Conclusions: Lenalidomide is effective in relapsed patients with MM after allo-SCT. Major toxicity is myelotoxicity, which required dose reduction in a majority of patients. With this background, a dose-finding study to determine the optimal lenalidomide dose as maintenance therapy after allo-SCT has already started.