Outcomes of the phase I/II REVLIRIT CLL-5 AGMT study in patients with CLL

On 4 June 2018, the results from the phase I/II REVLIRIT CLL-5 AGMT study were published in Annals of Hematology by Alexander Egle, Department of Internal Medicine III with Hematology and Medical Oncology, Oncologic center, Paracelsus Medical University Salzburg, Austria, and colleagues. This study evaluated the use of escalating doses of lenalidomide with fludarabine and rituximab (FR) followed by lenalidomide and rituximab maintenance in patients with previously untreated chronic lymphocytic leukemia (CLL).

Study Overview

• The study was non-randomized, multi-centre and open-label using the Arbeitsgemeinschaft
• Medikamentöse Tumortherapie (AGMT) trial consortium between September 2008 and November 2010
• N = 45 patients who were chemotherapy-naïve were included in this study. 58% were male and the median age of patients was 66 (range, 43–79)
• At the induction phase, patients received lenalidomide with FR for six cycles to determine a maximum tolerated dose (MTD). The next phase was maintenance with lenalidomide followed by rituximab
• The primary endpoint was determining the MTD of lenalidomide and FR
• Secondary endpoints included; efficacy, safety, risk factor dependency, minimal residual disease (MRD) and T-cell subset analysis

Key Findings

• At the induction phase MTD was determined as the tolerated dose when patients received this dose for at least two cycles consecutively. For 33% of the patients the MTD was 25mg of lenalidomide. In the maintenance phase 46% patients required dose reductions due to prolonged neutropenia
• At the induction phase, the most frequent adverse events (AEs) grade ≥3 included; neutropenia (71%) and grade 3 infection (6.7%)
• At the maintenance phase of (n = 40) evaluable patients the most frequent AEs grade 3 included; neutropenia (45%) and grade 4 neutropenia (27.5%)
• At induction, the overall response rate (ORR) was 89%
• Median follow-up of 78.7 months (95% CI, 76.7–80.7)
• Median progression-free survival (PFS) was 60.3 months
• Median overall survival (OS) was not reached
  • 5-year OS was 89%
• N = 39 patients were evaluable for MRD assessment from peripheral blood after induction. 56.4% of patients achieved MRD negativity, defined as less than 10^-3

The authors concluded that lenalidomide with FR was effective at induction responses and maintenance with lenalidomide and rituximab demonstrated long PFS with patients with previously untreated CLL. The authors also noted that due to recent efficacious novel treatments, they doubted the role of lenalidomide chemoimmunotherapy combinations in the treatment of previously untreated CLL.