Cyclosporine treatment of refractory T-cell lymphomas

Abstract

Background: Cyclosporine (cyclosporin A, CSA) prolongs the survival of transplanted organs by reducing the transcription of cytokines, especially interleukin-2, that are thought to mediate T-cell expansion and subsequent graft rejection. Recently, CSA has been suggested as a potentially effective agent in the treatment of T-cell neoplasms. As a result, a Phase II trial of CSA was done in patients with refractory T-cell lymphomas.

Methods: Patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who had disease progression after at least one previous therapy were eligible for participation. CSA was administered orally at a dose of 7.5 mg/kg twice daily, and the patients were followed for disease response and toxicity.

Results: A total of 16 patients were treated. Five patients had PTCL, and 11 had CTCL. Most patients were pretreated extensively with chemotherapy and/or radiation therapy. No responses occurred in patients with PTCL. Two of 11 patients with CTCL responded to therapy. Both patients who responded to CSA had recurrent disease that approached baseline levels within 1 week of discontinuing therapy. A second response occurred in both patients after reinstitution of therapy. Although most patients were removed from the study because of disease progression, renal toxicity was significant.

Conclusions: Most patients with refractory T-cell lymphomas did not respond to CSA, suggesting that these malignancies are not interleukin-2 dependent or, alternatively, that CSA did not reach its intracellular target. In the two responding patients, the pattern of repeated rapid regression of disease after CSA administration and subsequent rapid recurrence after a temporary halt in therapy suggested that CSA was cytostatic rather than cytocidal or that the clinical remissions were mediated by the antiinflammatory effects of the drug.