TY - JOUR
T1 - 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
AU - Pettitt, Andrew R.
AU - Jackson, Richard
AU - Carruthers, Stacey
AU - Dodd, James
AU - Dodd, Susanna
AU - Oates, Melanie
AU - Johnson, Gillian G.
AU - Schuh, Anna
AU - Matutes, Estella
AU - Dearden, Claire E.
AU - Catovsky, Daniel
AU - Radford, John A.
AU - Bloor, Adrian
AU - Follows, George A.
AU - Devereux, Stephen
AU - Kruger, Anton
AU - Blundell, Julie
AU - Agrawal, Samir
AU - Allsup, David
AU - Proctor, Stephen
AU - Heartin, Earnest
AU - Oscier, David
AU - Hamblin, Terry J.
AU - Rawstron, Andrew
AU - Hillmen, Peter
N1 - C18029/A5921, Cancer Research UK, United Kingdom
PY - 2012/5/10
Y1 - 2012/5/10
N2 - 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/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). 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. © 2012 by American Society of Clinical Oncology.
AB - 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/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). 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. © 2012 by American Society of Clinical Oncology.
U2 - 10.1200/JCO.2011.35.9695
DO - 10.1200/JCO.2011.35.9695
M3 - Article
C2 - 22493413
SN - 1527-7755
VL - 30
SP - 1647
EP - 1655
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 14
ER -
