Cutaneous Toxicity Associated with Pralatrexate in Cutaneous and Peripheral T-Cell Lymphoma

Pralatrexate is a folate analogue metabolic inhibitor that is approved for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) (O'Connor, O.A. et al. JCO. 2011 29: 1181–1189). More recently, pralatrexate has been investigated for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL) (Horowitz, S.M. et al. Blood. 2012 119: 4115–4122). The most common adverse event (AE) observed with pralatrexate has been mucositis with other reported AEs consisting of fatigue, nausea, and cutaneous toxicity.

We retrospectively analyzed the data of 22 patients who had received pralatrexate for a diagnosis of either PTCL or CTCL at our institution since 2010 in order to determine the incidence of cutaneous toxicity.

Of the 22 patients, 4 had a diagnosis of PTCL, 18 had CTCL. In the PTCL cohort, the median age was 66.5 with the median number of prior treatments (nonsystemic and systemic) being 2.75. One patient (25%) developed cutaneous toxicity which resulted in death. A skin biopsy revealed toxic erythema of chemotherapy and the skin lesions progressed to bullae and moist desquamation.

In the CTCL cohort, the median age was 60 with the median number of treatments being 5. A total of 14 patients (78%) developed cutaneous toxicity. The toxicity included worsening erythema, skin breakdown, ulceration, and pain at the CTCL lesion sites. The majority of patients (n= 10; 71%) developed the toxicity following cycle 1 week 1 of treatment. The development of cutaneous toxicity was seen in 8 patients at a dose of 15mg/m², in 3 patients at a dose of 10mg/m², and in 2 patients who underwent dose escalations to 17.5mg/m² and 20mg/m²respectively. Of those patients who developed cutaneous toxicity, 8 (57%) required the pralatrexate to be held and 2 patients (14%) required hospitalization and treatment with intravenous antibiotics for superimposed skin infection. The cutaneous toxicity observed was not associated with any other adverse event. Seven patients (39%) in the entire CTCL cohort developed grade I/II mucositis and 3 (17%) developed grade I diarrhea.

In 7 patients (50%) the pralatrexate was restarted at a lower dose, 3 patients were changed to an every other week dosing schedule, and 2 patients continued on pralatrexate with no change following resolution of their symptoms. Only 2 patients were not continued on pralatrexate following the cutaneous toxicity. In all 12 patients who were retreated with pralatrexate, cutaneous toxicity did not reoccur and the dose was able to be escalated. At the time of data analysis, 7 patients remained on treatment with pralatrexate while the remainder had discontinued therapy secondary to disease progression.

In this retrospective review, a high incidence of cutaneous toxicity was seen in CTCL patients who were treated with pralatrexate. The cutaneous toxicity might be interpreted as a “skin flare” since it may be concentrated at sites of CTCL lesions. The majority of patients developed the toxicity with the first dose and were able to continue on pralatrexate at a lower dose with eventual dose escalation. Based on data analysis, the “skin flare” is not dose dependent or associated with disease response.

Off Label Use: Pralatrexate is FDA approved for the treatment of relapsed or refractory peripheral T-cell lymphoma. Our abstract discusses its use, specifically the cutaneous toxicity observed, in both peripheral and cutaneous T-cell lymphoma. The use of pralatrexate in relapsed or refractory cutaneous T-cell lymphoma is off-label. Barbarotta:Genentech: Speakers Bureau; Allos: Speakers Bureau. Foss:Seattle Genetics: Consultancy; Celgene: Consultancy; Eisai: Consultancy; Celgene: Study Grant, Study Grant Other; Merck: Study Grant, Study Grant Other; Allos: Consultancy.