Efficacy of lenalidomide in patients with chronic lymphocytic leukemia with high-risk cytogenetics

Abstract

Patients with chronic lymphocytic lymphoma (CLL) with high-risk cytogenetics [del(11q)(q22.3) or del(17p)(p13.1)] have limited therapeutic options and their prognosis remains poor. This analysis was conducted to determine the clinical activity of lenalidomide in patients with high-risk disease. Relapsed/refractory patients with CLL enrolled in a phase II clinical trial who had del(11q)(q22.3) or del(17p)(p13.1) were included in this analysis. Patients received single agent lenalidomide for 21 days of the 4 week treatment cycle. The overall response rate among patients with high-risk cytogenetics was 38%, with 19% of patients achieving a complete response. Median progression-free survival was 12.1 months, which is higher than demonstrated with other agents in comparable patient populations. In addition, the estimated 2-year survival probability was 58%, demonstrating that the responses achieved with lenalidomide are durable, even in patients with CLL with high-risk disease with poor risk cytogenetics.

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

“…In vitro studies showed encouraging activity of single-agent forodesine and its combination with rituximab, regardless of ATM and TP53 status [32]. Lenalidomide has recently shown activity in relapsed patients with CLL with 11q or 17p deletions, with an ORR of 38%, CR of 19%, and median PFS of 12.1 months [33]. A Phase I and a subsequent Phase II study with the serine/threonine kinase inhibitor flavopiridol showed promising activity in pretreated patients with CLL; the ORRs for patients classified as 17p-, 11q-, or without these abnormalities were 48%, 57%, and 34%, respectively, and PFS was not significantly different among the cytogenetic groups (around 10 months) [34].…”

p53 and Notch signaling in chronic lymphocytic leukemia: clues to identifying novel therapeutic strategies

“…In those, the overall response rate is an encouraging 30-40% with some complete remissions, although progression-free survival is short. 78,79 There are ongoing trials of several p53-independent agents, some in patients who have had no previous treatment and some in combination regimes. There is a need to ensure transparency in reporting the results on trials on patients with p53 abnormalities and, as numbers are small, there is a further need to pool data on their responses where possible.…”

Outcomes of first-line treatment for chronic lymphocytic leukemia with 17p deletion

“…Of note, none of the 10 patients with del(17p) included in the 2 first-line studies of the immune-modulating agent, lenalidomide, achieved CR. 28,33,34 Given the retrospective nature of our analysis and the fact that it is not a randomized evaluation of treatment regimens, it is difficult to draw firm conclusions about the most appropriate firstline therapy for these patients, although it did not appear that we could identify a regimen that seemed to stand out above the others. In our analysis, higher CR/nPR rate was associated with "low burden" del(17p) by FISH.…”