Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia

Abstract

This study investigated the activity of lenalidomide in patients with relapsed/ refractory chronic lymphocytic leukemia (CLL). Lenalidomide was given at 10 mg daily with dose escalation up to 25 mg daily. Three patients (7%) achieved a complete response (CR), one a nodular partial remission, and 10 patients a partial remission (PR), for an overall response (OR) rate of 32%. Treatment with lenalidomide was associated with an OR rate of 31% in patients with 11q or 17p deletion, of 24% in patients with unmutated V H , and of 25% in patients with fludarabine-refractory disease. The most common toxicity was myelosuppression, and the median daily dose of lenalidomide tolerated was 10 mg. Plasma levels of angiogenic factors, inflammatory cytokines, and cytokine receptors were measured at baseline, day 7, and day 28. There was a dramatic increase in median interleukin (IL)-6, IL-10, IL-2, and tumor necrosis factor receptor-1 levels on day 7, whereas no changes were observed in median vascular endothelial growth factor levels (20 patients studied). According to our experience, lenalidomide given as a continuous treatment has antitumor activity in heavily pretreated patients with CLL. This trial is registered at http://www.clinicaltrials.gov as no. NCT00267059. (Blood. 2008;111: 5291-5297)

Thalidomide exerts distinct molecular antileukemic effects and combined thalidomide/fludarabine therapy is clinically effective in high-risk chronic lymphocytic leukemia

“…These results are in accordance with a recent study evaluating the use of lenalidomide in patients with CLL, which showed a response to treatment with immunomodulatory drugs (IMiDs) in high-risk patients with CLL. 22 Interestingly, in our study two out of four (50%) 17p-deleted refractory cases with CLL responded to thalidomide (reduction of WBC on day 7) as well as thalidomide/fludarabine therapy, suggesting that IMiDs may be effective in 17p-deleted patients with CLL. In addition, thalidomide/fludarabine therapy might also be considered in refractory patients with CLL.…”

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi

“…With its activity as a single agent or in combination, 11,15,[18][19][20][35][36][37][38] lenalidomide appears to be a strong candidate for inclusion in initial therapy of patients with aggressive Bcell non-Hodgkin's lymphoma. Furthermore, a recent study suggests that lenalidomide has improved activity in activated B-cell-like DLBCL compared with germinal center B-cell-like DLBCL.…”

Refractory chronic lymphocytic leukemia - new therapeutic strategies

“…7 % of the patients achieved CR, 10 % PR. 31 % of the patients with 11q-or 17p-deletion (combined) responded, 24 % of the patients with unmutated IGHV and 25 % with fludarabine refractory disease [34]. A subgroup analysis of the trial showed that lenalidomide is also effective in patients with high-risk CLL (combined 11q-or 17p-deletion).…”