T Regulatory Cells in Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with High Dose Methylprednisolone and Rituximab

Higher circulating T regulatory cell (Treg) numbers have been found in untreated patients with chronic lymphocytic leukemia (CLL) compared to healthy subjects and correlated with progressive disease as well as time to first treatment in low-risk patients [1]. Some agents can reduce Treg numbers in CLL patients, but there are no data on the prognostic role of Treg dynamics and patient outcome. We present data from the LT-CLL-001 study, in which the clinical benefit of dose-dense high dose methylprednisolone (HDMP) and rituximab (Rtx) combination in relapsed or refractory high-risk patients with CLL was evaluated [2]. During the study, the change of T regulatory cell frequencies was measured in relation to overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Twenty-nine CLL patients with clinically or biologically high-risk disease were included. Treg frequency was evaluated at screening, after three treatment courses, and at the end of therapy. Significant reduction of the median frequencies of Treg during treatment was observed: median (range) of Treg0-3 after three treatment courses was 2.14% (-1.84%- 9.42%), p < 0.001 and median (range) of Treg0-6 was 1.01% (-2.95%- 8.35%, p = 0.004). Patients with deeper Treg reduction between screening and three treatment courses had significantly better PFS and OS (Table 1 & 2). Our data for the first time show that HDMP and Rtx combination reduces Treg frequency in pretreated CLL patients. Early and deeper Treg reduction is an independent prognostic factor for longer PFS and OS. (ClinicalTrials.gov identifier: NCT005 58181).