Interferon Alfa-2a Combined With Phototherapy in the Treatment of Cutaneous T-Cell Lymphoma

Abstract

Escalating doses of recombinant interferon alfa-2a (Roferon-A), administered intramuscularly three times weekly, combined with psoralen plus ultraviolet light irradiation (PUVA), were tested in a phase I trial for the therapy of patients with cutaneous T-cell lymphomas (CTCL). Interferon doses were escalated in groups of three patients from 6 million to 30 million IUs three times weekly. Disease stages ranged from IB to IVB. Eighty percent of the patients entered in this trial had failed at least one prior therapy. Complete remissions were obtained in 12 of 15 patients, and partial responses were seen in two of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 13 months (range, 3-15+). All patients who responded have been maintained on therapy. The dose-limiting toxic effects were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). These side effects were reversible with a decrement in dose or discontinuation of the interferon. No patient tolerated 30 million IU of the interferon for extended periods; the maximally tolerated dose was 18 million IU. Interferon plus PUVA appears to be a highly effective regimen for the treatment of patients with CTCL. Phase II studies investigating this combination, using 18 million IU of interferon alfa-2a three times weekly, should be undertaken to expand these findings, and to attempt to reduce the toxic effects associated with this therapy.

Management of cutaneous T cell lymphoma

“…Psoralens and ultraviolet A are usually well tolerated, although interferon is limited by side effects related to the dose 2. Like Mostow et al,4 however, we found that a regimen of low dose interferon was extremely well tolerated, even by an 89 year old woman.…”

Sézary syndrome: Immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC)

“…61,67 Interferon alfa in combination with psoralen plus ultraviolet (UV) A (PUVA) has shown efficacy in E-MF (blood involvement unspecified) 56,68-70 but there was not been a uniform response in the two patients with SS reported. 71,72 Interferon in combination with retinoids (isotretinoin, etretinate, bexarotene) has been noted to be effective in late-stage MF/SS 73-77 but, to our knowledge, there are no studies where the combination is compared with monotherapy alone and none where the results in SS are specifically addressed. Patients with SS treated with a combination of interferon alfa and pentostatin 78 or interferon alfa and fludarabine 79 demonstrated ORs but the overall response rate (RR) in all patients with MF thus treated (41% and 51%, respectively) was not higher than that seen in other studies with interferon alone.…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Responses, which may be achieved within a few months, are observed in patients with tumor-stage MF and SS. Furthermore, interferon-alpha may be successfully combined with a number of other therapeutic modalities, including PUVA, bexarotene, chemotherapy and ECP, which are frequently utilized in the management of these patients [289][290][291][292][293][294][295][296][297][298][299][300][301][302]. For example, in a cohort of 51 patients (42 of which had advancedstage disease) treated with single-agent, low-dose, interferon-alpha, responses were observed in 34 (67%), 21 (41%) of which were complete and maintained long-term in nine patients [288].…”