(ChemotherapyAdvisor) – For patients with chronic lymphocytic leukemia (CLL) and deletion of TP53, alemtuzumab plus methylprednisolone is a highly effective induction regimen, final results of the National Cancer Research Institute CLL206 multicenter Phase 2 trial reported in the Journal of Clinical Oncology online April 9.
Deletion of TP53 on chromosome 17p (17p—) is associated with the worst prognosis. The study was designed to improve treatment of TP53-defective CLL; to date, TP53 defects have not been associated with anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone resistance.
A total of 39 patients with TP53-deleted CLL received up to 16 weeks of treatment with alemtuzumab 30mg three times weekly and methylprednisolone 1g/m2 for five consecutive days every four weeks. Median age was 61.5 years (range, 34–82); 56% were men and 46% were Binet stage C; 10 patients had lymph nodes greater than 5cm. Seventeen patients (44%) were treatment-naïve and 22 (56%) had previously received one to four lines of therapy.
Overall response rate was 85% and complete response rate, including with incomplete marrow recovery, 36%. Median progression-free survival (PFS) was 11.8 months and median overall survival (OS), 23.5 months. For treatment-naïve patients, overall response rate was 88% and complete response rate, 65%; median PFS and OS were 18.3 months, and 38.9 months, respectively.
Grade 3/4 hematologic toxicity occurred in 67% of patients and glucocorticoid-associated toxicity in 23%. Grade 3/4 infection was observed in 51% of the overall cohort and in 29% of patients <60 years of age. Treatment-related mortality was 5%.
“Alemtuzumab plus methylprednisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL,” they wrote. “The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide.”
They noted that these findings, supported by preliminary results of the German/French CLL2O trial of alemtuzumab plus dexamethasone, “indicate that the clinical course of 17p— CLL might be improved by a more rational approach to induction therapy that takes into account molecular mechanisms of drug resistance.”