NCRN CLL207 STUDY OF ALEMTUZUMAB CONSOLIDATION IN
chronic lymphocytic leukaemia: REPORT OF THE PLANNED INTERIM ANALYSIS
Authors
P. Hillmen,1 D.R. Cohen,2 C. Dearden,3 G. Follows,4 W.M. Gregory,2 A.F. Smith,2 E.J. Skinner,2 A. Critchley,1 A.C. Rawstron,1 C.D. Fegan,5 H. McCarthy,6 C.F. Pocock7
Abstract
Backgrounds. The duration of remission in patients with chronic lymphocytic leukaemia (CLL) is highly dependent on the level of minimal residual disease (MRD) that remains at the end of therapy, regardless of the therapy used to achieve remission. The conversion of remissions from MRD positive to negative should prolong remissions and survival. Several small studies have used alemtuzumab as consolidation therapy following conventional chemotherapy with good efficacy but concerns over toxicity; primarily due to immune suppression and infections. The dose and timing (i.e. interval between prior chemotherapy and alemtuzumab) seem to be critical. Aims. The NCRN CLL207 Trial is designed to assess alemtuzumab consolidation post-chemotherapy in a phase II setting. Herein are the results from a planned interim analysis on the primary endpoints: eradication of MRD and assessment of safety. 25 patients have completed treatment, with a maximum of 54 patients planned to be recruited. Methods. The alemtuzumab dose of 30 mg was administered subcutaneously 3 times a week for 6 weeks, at which time patients had a bone marrow to assess response. MRD negative patients and non-responders stopped therapy; MRD positive patients with a significant response compared to pre-alemtuzumab continued therapy for a further 6 weeks. MRD was assessed in peripheral blood and marrow using 6-colour flow cytometry with a 0.01% detection limit. All patients received prophylaxis with co-trimoxazole (or equivalent) and aciclovir as well as weekly CMV monitoring by PCR. Results. Of the 25 patients who have completed alemtuzumab therapy, 23 had received fludarabine combinations as the latest therapy and 4 had received rituximab combined with fludarabine-based treatment. Alemtuzumab was stopped in 2 patients before week 6 due to toxicity, 19 patients received 6-8 weeks of treatment and 4 patients received a 12-week course. 8 (32%) patients required G-CSF during alemtuzumab. There were 12 reported SAE’s in 10 (40%) patients, most of which were infections. 3 patients have died: one as a direct result of a treatment-related SAE (parainfluenza); one due to treatment-related MDS presumed to be related to prior therapy; and one due to progressive CLL. Positive CMV PCRs were detected in 12 (48%) patients, all of whom were successfully treated with pre-emptive antiviral therapy. After alemtuzumab, of 24 patients with known results, 18 (75%) became MRD negative, 4 (16.7%) remained MRD positive and 2 (8.3%) were not evaluable. 8 out of 9 (89%) patients who were MRD positive CR’s at initiation of alemtuzumab became MRD negative. 10 out of 15 (67%) patients who were MRD positive PR’s at initiation of alemtuzumab became MRD negative. Conclusions. 18 of 24 patients (75%) treated with alemtuzumab as consolidation therapy achieved MRD negative responses in their marrows. Such an approach is associated with mainly infective toxicities, which are largely manageable with recommended prophylaxis and close monitoring. These results support the continued investigation of alemtuzumab consolidation in CLL but primarily within a clinical trial setting and with appropriate monitoring of patients.