Title
A phase 2 study of lenalidomide and dexamethasone in previously untreated patients with chronic lymphocytic leukemia (CLL)
Publication Date
2018
Journal Title
Leuk Lymphoma
Abstract
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Lenalidomide has anti-tumor activity in CLL but can be complicated by tumor lysis syndrome (TLS) and tumor flare (TF). In our previous study using low-dose lenalidomide in treatment-naive CLL, TLS was averted but TF remained frequent and complete responses (CR) were rare, despite treatment to progression. The addition of dexamethasone may mitigate TF and enable lenalidomide dose escalation, achieving durable response without long-term use. In this phase 2 trial, 31 treatment-naive CLL patients received lenalidomide (target 25mg daily) plus dexamethasone for a finite 18 cycles. No patients developed TLS and TF was infrequent. Overall responses were 74.2% (CR 9.7%) and median progression-free survival 27 months. Cereblon-binding proteins IKZF1 and IKZF3 were largely downregulated, with associated increased IRF4 levels. We therefore report that lenalidomide plus dexamethasone can achieve durable responses in a subset of patients without continuing therapy until progression. Upregulation of IRF4 may contribute to anti-CLL activity of immunomodulatory agents. This trial was registered at www.clinicaltrials.gov as NCT01133743.
Volume Number
60
Issue Number
4
Pages
980-989
Document Type
Article
Status
Faculty
Facility
School of Medicine
Primary Department
Molecular Medicine
Additional Departments
General Internal Medicine
PMID
DOI
10.1080/10428194.2018.1508669