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

作者：Pettitt Andrew R^*; Jackson Richard; Carruthers Stacey; Dodd James; Dodd Susanna; Oates Melanie; Johnson Gillian G; Schuh Anna; Matutes Estella; Dearden Claire E; Catovsky Daniel; Radford John A; Bloor Adrian; Follows George A; Devereux Stephen; Kruger Anton; Blundell Julie; Agrawal Samir; Allsup David; Proctor Stephen; Heartin Earnest; Oscier David; Hamblin Terry J; Rawstron Andrew; Hillmen Peter

来源：Journal of Clinical Oncology, 2012, 30(14): 1647-1655.

DOI：10.1200/JCO.2011.35.9695

Purpose %26lt;br%26gt;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. %26lt;br%26gt;Patients and Methods %26lt;br%26gt;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/m(2) 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). %26lt;br%26gt;Results %26lt;br%26gt;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%. %26lt;br%26gt;Conclusion %26lt;br%26gt;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.

• 出版日期2012-5-10