Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial
- 10 May 2012
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 30 (14), 1647-1655
- https://doi.org/10.1200/jco.2011.35.9695
Abstract
Purpose: In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination. Patients and Methods: Thirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m2 for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free survival (PFS) and overall survival (OS). Results: The overall response rate, complete response rate (including with incomplete marrow recovery), median PFS, and median OS were 85%, 36%, 11.8 months, and 23.5 months, respectively, in the entire cohort and 88%, 65%, 18.3 months, and 38.9 months, respectively, in previously untreated patients. Grade 3 to 4 hematologic and glucocorticoid-associated toxicity occurred in 67% and 23% of patients, respectively. Grade 3 to 4 infection occurred in 51% of the overall cohort and in 29% of patients less than 60 years of age. Treatment-related mortality was 5%. Conclusion: Alemtuzumab plus methypredisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL. The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide.Keywords
This publication has 48 references indexed in Scilit:
- Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trialThe Lancet, 2010
- The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registryLeukemia, 2010
- From pathogenesis to treatment of chronic lymphocytic leukaemiaNature Reviews Cancer, 2009
- Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trialBlood, 2009
- Allogeneic Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic Leukemia With 17p Deletion: A Retrospective European Group for Blood and Marrow Transplantation AnalysisJournal of Clinical Oncology, 2008
- Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelinesBlood, 2008
- Fludarabine, Cyclophosphamide, and Mitoxantrone as Initial Therapy of Chronic Lymphocytic Leukemia: High Response Rate and Disease EradicationClinical Cancer Research, 2008
- Efficacy of rituximab in combination with steroids in refractory chronic lymphocytic leukemiaLeukemia & Lymphoma, 2008
- Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemiaBlood, 2006
- Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletionsBlood, 2004