Regimen Shows Benefit for Advanced Melanoma
Conditioning treatment allows cytotoxic T cells to survive longer
TUESDAY, March 6 (HealthDay News) -- A minimal, less-toxic conditioning treatment with cyclophosphamide, that allows cytotoxic T-lymphocyte clones to survive for longer, shows some clinical benefit in patients with refractory, metastatic melanoma, according to a study published online March 5 in the Proceedings of the National Academy of Sciences.
To determine whether high-dose cyclophosphamide conditioning could sufficiently enhance the survival of adoptively transferred T cells, with limited toxicity, Aude G. Chapuis, M.D., from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues treated 11 patients with refractory, progressive metastatic melanoma with cyclophosphamide, infused them with autologous antigen-specific CD8+ cytotoxic T lymphocyte clones, and then administered low- or high-dose interleukin-2.
Of 10 evaluable patients, the researchers found that one achieved complete remission and five had stable disease at eight weeks, although all patients except the patient who achieved complete remission eventually progressed by 12 to 19 weeks. Patients who received low-dose interleukin-2 had a transient expansion of the infused cells, which localized to nonvascular compartments such as skin and lymph nodes, and on-target autoimmune skin toxicity. The infused cells had characteristics of effector memory cells, and those cytotoxic T-lymphocytes which persisted long term acquired phenotypic and/or functional properties of central memory T cells.
"The use of a T-cell product composed of a clonal population of antigen-specific cytotoxic T lymphocytes afforded the opportunity to demonstrate phenotypic and/or functional conversion to a central memory type with the potential for sustained clinical benefit," Chapuis and colleagues conclude.