Final Results from the CLL20 Study: Alemtuzumab plus Dexamethasone in Very High–Risk Patients with CLL
CLL20 was a cooperative French/German open-label study aimed at evaluating the response of patients with CLL who had del17p or were refractory to fludarabine-based regimens, to the combination of alemtuzumab plus dexamethasone (AD) as induction therapy before consolidation with alemtuzumab maintenance or allogeneic SCT (Stilgenbauer S, et al. Blood. 2014;124. Abstract 1991).
The induction treatment of 131 allogeneic SCT-eligible patients consisted of subcutaneous alemtuzumab plus oral dexamethasone on 28-day cycles plus prophylactic pegfilgrastim. If at least a stable disease response was achieved after 3 cycles, the patients were treated with consolidation consisting of allogeneic SCT or alemtuzumab maintenance for up to 2 years. As shown in the Table, patients were divided into 3 cohorts—those with del17p who were being treated with AD as first-line therapy, those with del17p who had relapsed after initial induction therapy, and those who were refractory to fludarabine-based or similar therapies. All 3 cohorts were characterized by high-risk baseline disease features (Table).
The ORRs were high in all 3 cohorts, but complete remissions were observed primarily in the first-line del17p group, which also exhibited significantly better PFS and OS outcomes. During induction, the hematologic adverse events were as shown in the Table; the nonhematologic events were predominantly of a minor grade.
Consolidation consisted of alemtuzumab maintenance in 37% of the patients and allogeneic SCT in 25% of the patients who had stable disease after induction therapy. When comparing PFS between alemtuzumab maintenance and allogeneic SCT, patients experienced 84% and 48% events, respectively, significantly favoring allogeneic SCT (P = .002). Moreover, during alemtuzumab maintenance, grade 3/4 neutropenia (47%) and thrombocytopenia (12%) were observed, with 10% to 17% serious noncytomegalovirus infections observed in the 3 cohorts.
Thus, AD followed by alemtuzumab maintenance or allogeneic SCT demonstrated high response rates in what the authors describe as “ultra high-risk patients with CLL. In patients with del17p who received first-line treatment with AD, the results are comparable with standard FCR therapy. Allogeneic SCT offers superior disease control compared with alemtuzumab maintenance after induction with AD. These data may provide a new benchmark for treating ultra high–risk patients with CLL.