• Andrew R Pettitt, Richard Jackson, Stacey Carruthers, James Dodd, Susanna Dodd, Melanie Oates, Gillian G Johnson, Anna Schuh, Estella Matutes, Claire E Dearden, Daniel Catovsky, John A Radford, Adrian Bloor, George A Follows, Stephen Devereux, Anton Kruger, Julie Blundell, Samir Agrawal, David Allsup, Stephen Proctor, Earnest Heartin, David Oscier, Terry J Hamblin, Andrew Rawstron, and Peter Hillmen.
• University of Liverpool, Liverpool, UK. arp@liverpool.ac.uk
• J. Clin. Oncol. 2012 May 10; 30 (14): 1647-55.

PurposeIn 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 MethodsThirty-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).ResultsThe 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%.ConclusionAlemtuzumab 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.

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