Original Manuscript
Leukemia (2004) 18, 1093–1101. doi:10.1038/sj.leu.2403354 Published online 8 April 2004
Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission – experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG)
Presented, in part, at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31–June 3, 2003, and the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 6–9, 2003.
Supported by a research grant of Schering AG, Berlin and MedacSchering Onkologie, Germany. VH sequencing was supported by a research grant from the Else Kröner-Fresenius Stiftung, Germany.
C-M Wendtner1,6, M Ritgen2, C D Schweighofer1,6, G Fingerle-Rowson1,6, H Campe3, G Jäger3, B Eichhorst1, R Busch4, H Diem5, A Engert6, S Stilgenbauer7, H Döhner7, M Kneba2, B Emmerich8, M Hallek1,6 and the German CLL Study Group (GCLLSG)
- 1Klinikum Grosshadern, Medical Clinic III, Ludwig-Maximilians-University, Munich, Germany
- 2Medical Clinic II, University Hospital, Kiel, Germany
- 3Max-von-Pettenkofer-Institute, Ludwig-Maximilians-University, Munich, Germany
- 4Institute of Medical Statistics and Epidemiology, Technical University, Munich, Germany
- 5Clinical Chemistry, Ludwig-Maximilians-University, Munich, Germany
- 6Medical Clinic I, University Hospital, Cologne, Germany
- 7Medical Clinic III, University Hospital Ulm, Germany
- 8Medizinische Klinik Innenstadt, Ludwig-Maximilians-University, Munich, Germany
Correspondence: Prof Dr Michael Hallek, Klinik I für Innere Medizin, Klinikum der Universität zu Köln, Joseph-Stelzmann-Strasse 9, D-50924 Köln, Germany. Fax: +49 221 478 5455
Received 13 November 2003; Accepted 1 March 2004; Published online 8 April 2004.
Abstract
Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis IV; four CMV reactivations III requiring i.v. ganciclovir; one pulmonary tuberculosis III; one herpes zoster III) were successfully treated and not associated with cumulative dose of alemtuzumab. In the observation arm, one herpes zoster infection II and one sinusitis I were documented. At 6 months after randomization, two patients in the alemtuzumab arm converted to CR, while three patients in the observation arm progressed. After alemtuzumab treatment, five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive (P=0.048). At 21.4 months median follow-up, patients receiving alemtuzumab showed a significant longer progression-free survival (no progression vs mean 24.7 months; P=0.036). In conclusion, a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL, but a safe treatment regimen needs to be determined.
Keywords:
CLL, alemtuzumab, consolidation, survival, MRD, CMV
