Washington, DC—Alemtuzumab is the most effective first-line therapy for T-cell prolymphocytic leukemia (T-PLL), according to a presentation at the Peripheral T-cell Lymphoma Forum.
Alemtuzumab is effective when administered alone or in combination with purine analogs, should be administered intravenously as opposed to subcutaneously, and is also effective as a second-line therapy in T-PLL, said Claire Dearden, MD, FRCP, FRCPATH, of The Royal Marsden Hospital.
Dr Dearden also recommended that T-PLL patients be considered for allogeneic stem cell transplant versus autologous stem cell transplant during first remission after alemtuzumab treatment to ensure long-term survival. Once patients relapse, she said, there is no second chance for transplant.
Dr Dearden discussed results she and her colleagues observed in T-PLL patients treated with alemtuzumab in the last 10 years. Some patients were previously untreated, and others underwent chemotherapy prior to receiving alemtuzumab.
In 38 previously treated patients, 62% achieved a complete response (CR). When 16 untreated patients received alemtuzumab intravenously, 88% achieved a CR. In comparison, 11% of patients achieved a CR after subcutaneous administration. This group was rescued with intravenous administration and pentastatin.
These results suggest that alemtuzumab should be administered intravenously rather than subcutaneously to achieve substantial efficacy. The use of intravenous alemtuzumab resulted in survival greater than 2 years.
Dr Dearden also communicated results in 26 T-PLL patients who received stem cell transplant following response to alemtuzumab. Fifteen patients received autograft, and 11 received allograft.
Fifty-five percent of patients who received allograft are still alive, as are 40% of patients who received autograft. Allografted patients also have a lower relapse rate than autografted patients, at 27% vs 53%, respectively. However, the rate of transplant-related mortality is higher in allografted patients, at 27% vs 14%, respectively.
Dr Dearden pointed out that allogeneic stem cell transplant is usually an attractive option. However, because patients with T-PLL tend to belong to an older age group, the procedure often involves a high morbidity and mortality rate.
Dr Dearden also discussed the cytogenetics that uniquely characterize T-PLL. She observed that 75% of cases have the same break point on chromosome 14. These include the inversion (14)(q11q32), the translocation t(14;14)(q11;q32), and the translocation t(X;14)(q28;q11).
Other recurrent changes involve chromosome 8, where 8 translocations have been noted. Significant molecular abnormalities also include the expression of ATM on 11q23, MTCP1 on Xq28, and TCL1a on 14q32.
The oncogene products, most commonly TCL1a, form stabilizing complexes with Akt. They activate Akt by complexing and inducing phosphorylation, downregulating pro-apoptotic control, and ensuring proliferation and survival of the T-PLL cell.
There is also an enrichment of deregulated genes on chromosome 8. NBS1 stimulates the Akt pathway. The gene UPD causes a loss of tumor suppressor gene regulation. ANK-1 is involved in motility and may explain the skin lesions and peritoneal involvement observed in T-PLL.
Dr Dearden suggested that many chromosomal and genetic abnormalities lead to a common upregulation of Akt. Therefore, using Akt or HSP 90 inhibitors may be viable approaches to future treatment.
The Peripheral T-cell Lymphoma Forum took place September 18-20.
