Therapeutic Update: Update on Cutaneous and Systemic Therapy for Primary Cutaneous T Cell Lymphoma, Mycosis Fungoides

open label study, half (3/6) of the patients demonstrated both clinical and histological clearance of their index MF lesion treated with topical imiquimod 5% cream 3 times per week.⁷ In a small case series of 4 patients with recalcitrant early stage disease, all patients experienced complete clinical clearance after an average of 7 months of treatment 3 times per week with 5% imiquimod.⁸ Additionally, 3 of the 4 patients also demonstrated histologic clearance (single post treatment biopsy performed).⁸ After 10 days of daily application, Imiquimod 5% cream was also shown to induce clinical clearance of recalcitrant MF facial plaques in a patient treated with photochemotherapy (PUVA: 8-methoxypsoralen and UV-A light).⁶ Side effects of imiquimod 5% cream include irritation, erythema, and ulceration and patients who develop marked irritation may be more likely to develop histologic clearance of MF lesions.^6,7,8 One patient actually reported resolution of pruritus after 6 weeks of topical therapy.⁸

Although not yet available for commercial use, a recent phase I trial of Resiquimod gel has demonstrated benefit for the treatment of early stage and recalcitrant MF plaques. Resiquimod is also an imidazoquinoline immunomodulator and is an agonist of both TLRs 7 and 8.⁹ Unlike imiquimod, resiquimod is a potent activator of myeloid dendritic cells, which express TLR 8 and are the dominant dendritic cell population in inflamed as well as healthy human skin.9 In humans, TLR 7 is only expressed by plasmacytoid dendritic cells (PDC), which are rare in healthy skin however prominent in inflamed skin and skin cancers.⁹ In the above trial, patients with stage IA-IIA MF and folliculotropic MF, most with refractory disease despite multiple skin-directed and systemic therapies, were treated with either Resiquimod 0.03% gel or 0.06% gel three times per week for 8 weeks.⁹ In total, 75% of patients had significant clinical improvement of treated lesions.⁹ Unexpectedly, 92% of patients demonstrated >50% improvement in untreated lesions and 25% of patients treated with Resiquimod 0.06% gel had complete responses, one of which included a patient with folliculotropic MF.⁹ Side effects of resiquimod gel are most commonly skin irritation and erosion however fever, headache, and myalgias were also reported. ⁹ Of note, 2/5 patients with intractable diffuse pruritus in the setting of folliculotropic MF had complete resolution by treatment week 8.⁹

Patients with central nervous system (CNS) involvement of MF have poor survival, with death occurring usually between 3-6 months.10 Overall 5 year survival of stages II, III and IV MF are 49%, 40% and 0% respectively.11 Temozolomide is an oral imidazotetrazine alkylating agent and a derivative of dacarbazine.10 In a phase II trial, temozolomide demonstrated moderate activity against stage IIB-IVA MF with an overall response rate of 27%.12 In a small case series involving 4 MF patients with CNS involvement, temozolomide was given orally at 200mg/m2 once daily for five days, repeated every 28 days for