Retreatment with Alemtuzumab after a First, Successful Alemtuzumab Treatment in B-CLL.
Authors: Fiegl Michael , Falkner Florian , Falkner Andreas , Zojer Niklas , Fridrik Michael , Hopfinger Georg , Stauder Reinhard , Gunsilius Ebehard , Kantner Johanna , Erdel Martin , Tinhofer Inge , Gastl Guenther , Greil Richard ,   the Austrian Cooperation on MabCampath Use in CLL
Published: November 2019

Abstract
Alemtuzumab is the standard therapy for treatment of patients with relapsed/refractory B-CLL, and significant responses have also been documented in the front-line CLL setting. We and others have demonstrated, in controlled studies and retrospective surveys, that heavily pretreated patients who achieve a complete response (CR) or partial response (PR), or even stable disease (SD), as defined by the National Cancer Institute (NCI) criteria, benefit in terms of quality of life and prolonged overall survival (OS). This is probably due to the fact that response is of long duration and that, in many cases, effective re-treatment is feasible. We analysed which treatments were used following a first course of alemtuzumab in CLL (Fiegl et al. Cancer2006;107:2408–16), and found that alemtuzumab, alone or in combination, was the most frequently used drug for re-treatment. Here we present updated data in 26 CLL patients re-treated with alemtuzumab. Seventeen patients were male (65%), had B-CLL (n=23), B-CLL with more than 15% prolymphocytes (n=2), or CLL with Richter’s transformation (n=1). The median number of previous therapies including the first course of alemtuzumab was 4 (range, 2–12), and 15 cases (58%) were fludarabine-refractory. At the start of re-treatment, the majority of patients had Rai stage 4 disease. Fluorescence in situ hybridization (FISH) cytogenetics according to Dohner’s classification were available in 13 patients, and 5 patients had a high risk anomaly (17p deletion). The median time interval between last dose of alemtuzumab and start of alemtuzumab re-treatment was 10.2 months (1.7–28.3 months). Response evaluation according to NCI criteria was available in 17 patients. Alemtuzumab re-treated patients had PR, SD, and progressive disease (PD) rates of 53%, 18%, and 18%, respectively. In 12% response could not be evaluated because of early death. Survival rates were available for all 26 patients. The median OS since start of alemtuzumab re-treatment was 16.7 months. This favourable survival time underscores the fact that patients receiving alemtuzumab re-treatment are selected because they benefited from the previous course of alemtuzumab. There was a dramatic difference in outcome depending on whether alemtuzumab re-treatment was necessary earlier or later: median OS was 8.4 months in patients who had to be re-treated within 10.3 months after last dose of initial course of alemtuzumab, whereas median OS was not reached in patients retreated after a longer interval (P=0.001). OS was inferior in cytogenetically poor risk patients (17.8 months in 17p-deleted patients vs. “not reached” in patients with 13q deletion, trisomy 12, or normal karyotype; P=0.01). There was no difference in OS in fludarabine-refractory patients. Re-treatment was well tolerated, with moderate toxicity. In conclusion, we hereby demonstrate that B-CLL patients who have been treated successfully with alemtuzumab may benefit profoundly from a second course of alemtuzumab, especially if there is a prolonged interval between the treatments, and a favourable cytogenetic profile is present.