Activity of interferon-alpha and isotretinoin in patients with advanced, refractory lymphoid malignancies

Interferon-alpha (IFN-alpha) and retinoids have shown nonoverlapping toxicity and each has shown antitumor activity in patients with lymphoma. The aim of the current study was to assess the toxicity, safety, and efficacy of IFN-alpha combined with isotretinoin in patients with advanced, refractory lymphoid malignancies.

Adults with biopsy-proven advanced lymphoid malignancy were treated. Patients with compromised bone marrow function (platelet counts as low as 30 x 10(9)/L) were eligible. Treatment was comprised of IFN-alpha at a starting daily dose of 3 mega units subcutaneously and isotretinoin orally starting at a dose of 1 mg/kg daily in 2 divided doses.

Forty-four patients were evaluable. Their median age was 57 years (range, 18-82 years). Eighteen patients had advanced cutaneous T-cell lymphoma, 6 patients had peripheral T-cell lymphoma, 14 patients had Hodgkin disease, and 6 patients had a variety of other lymphoid malignancies. Patients with Hodgkin disease had received a median of 6 previous therapies (range, 3-12 therapies) and patients with other lymphoid malignancies had received a median of 4 previous therapies (range, 1-9 therapies). The median duration of treatment was 4 months (range, 0.25-38 months). The overall response rate was 38.6% (complete response in 5 patients [11.3%] and partial response in 12 patients [27.3%]). The median response duration was 3 months (range, 1-95+ months). The most common toxicities were low-grade fever, flu-like symptoms, and fatigue (IFN-alpha effects); dry mouth and skin and hypertriglyceridemia (cis-retinoic acid effects); and thrombocytopenia (which generally occurred in patients with low baseline platelet counts).

IFN-alpha and isotretinoin combination therapy had antitumor activity and was well tolerated in heavily pretreated patients with lymphoid malignancies.