ORLANDO – Alemtuzumab treatment for 6 weeks following chemotherapy eliminated detectable levels of minimal residual disease in 83% of chronic lymphocytic leukemia patients in a phase II study presented at the annual meeting of the American Society of Hematology.
Previous studies have shown that the length of remission in chronic lymphocytic leukemia (CLL) patients depends on the level of minimal residual disease (MRD) at the end of therapy, regardless of the therapeutic regimen, said Dr. Abraham Varghese of St. James’s University Hospital in Leeds, England. Additional studies have shown that alemtuzumab (Campath) can be used as a consolidation therapy after chemotherapy in these patients, but toxicity remains a concern.
To assess the response of CLL patients to alemtuzumab consolidation, Dr. Varghese and his colleagues in the U.K. National Cancer Research Institute’s CLL trials subgroup conducted the prospective National Cancer Research Network CLL207 trial in 47 patients who received alemtuzumab for at least 6 weeks, starting at 6-24 months after chemotherapy. The patients had undergone one to four previous therapies; 51% had complete responses, and the remaining 49% had partial responses. The average age of the 35 men and 12 women was 58 years. About half had received one prior therapy, and 30% had received two therapies. All but one patient had prior fludarabine. The next most common treatment was rituximab, which nine patients (19%) had received.
Overall, 39 patients (83%) were MRD negative at the end of alemtuzumab treatment. At 6 months after treatment, 20 patients were MRD negative, and at 12 months after treatment, 13 patients remained negative, which suggests improved odds for long-term remission, especially in patients who were MRD negative at 6 weeks.
Prior to alemtuzumab treatment, 24 patients were in complete remission and 23 were in partial remission. In the complete remission group, 22 were MRD negative at the end of treatment, 15 were negative 6 months after treatment, and 8 were negative 12 months after treatment. In the partial remission group, 17 patients were MRD negative at the end of treatment, 5 were negative 6 months after treatment, and 5 were negative 12 months after treatment.
Dr. Varghese reported 351 adverse events, 23 of which were severe. Four patients (9%) experienced unacceptable severe adverse reactions: pneumocystis pneumonia that lasted for 1.3 days; Epstein-Barr virus–driven, high-grade B-cell lymphoma of the bowel leading to hematemesis; parainfluenza leading to death; and EBV-driven, high-grade B-cell lymphoma leading to death. Serious adverse events included 14 infections, 3 hematologic disorders, 2 general disorders and administration site conditions, and 1 cardiovascular disorder, Dr. Varghese said.
Although the toxicity was significant, the study results are encouraging, he said. All 47 patients who received treatment were part of the final analysis. In addition, the target number of patients who were negative for MRD in the study was 14, but 39 patients in the study achieved MRD negativity, he noted.
The results suggest that alemtuzumab consolidation therapy should be further studied in a randomized phase III trial, Dr. Varghese said. A randomized phase III trial will compare alemtuzumab consolidation with observation in CLL patients.
Dr. Varghese had no financial conflicts to disclose. Several of his coauthors disclosed receiving honoraria or research funding, serving on the board of directors or advisory committee, or receiving patent and royalty funds from multiple companies including Genzyme, which makes Campath.