Mexican Patient with Refractory Mycosis Fungoides Successfully Treated with Pralatrexate at Low Doses: Case Report
Authors: Lopez Jose R 
Published: October 2019

Abstract
Introduction
Primary cutaneous lymphomas (PCL) are defined as non-Hodgkin lymphomas. They are found in the skin without an extra primary cutaneous location at the moment of diagnosis1. Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common subtypes of cutaneous T-cell lymphomas, MF represents less than 1% of the total number of non-Hodgkin lymphomas1,2,3; however, it is the most common cutaneous lymphoma2. It usually has an indolent course and good prognosis when identified in its early stages3. Therefore, treatment should be reaching the optimal benefit with minimizing the toxicity as much as possible. The therapeutic approaches for patients with PCL depend on the disease stage; skin-directed therapies are generally used, with systemic treatments reserved for patients with relapsed or more extensive disease. However durable remissions off-therapy are uncommon in MF/SS and, historically, more aggressive first-line approaches have not resulted in improved outcomes, but are associated with increased toxicity3. The moderate response rates and frequent lack of durable responses to current therapies for PCL underline the need for additional effective and tolerable treatments. This case represent the first Mexican patient treated successfully with low doses of pralatrexate as monotherapy, achieving almost complete response.
Case
The patient is a 40 years old male with history of skin tumoral lesions that previously was diagnosed as primary anaplastic lymphoma, however, in a skin biopsy and immunohistochemistry it was identified Mycosis fungoides.
The classical type of MF has 4 stages: patch, plaque, tumoral and erythroderma or Sézary syndrome. Of them, the most common is the patch/plaque MF, which presents with extremely pruritic, erythematous macules and patches with telangiectasias and atrophy in the "bathing trunk" distribution2. In this case initially the patient presented with plaque and tumoral lesions in 45% of body surface area. Mostly in thorax, face and arms, highly symptomatic and aesthetically unpleasant.
He was initially managed with PUVA and topical corticosteroids, followed by CHOP-R with bad response to both treatments. The treatment was changed to bortezomib and interferon with limited response. Then it was decided to change treatment to pralatrexate at low doses (according to Mexican guidelines of NHL treatment) 15 mg/m2 as monotherapy in cycles of 10 weeks (6 weeks on treatment and 4 off treatment). After the initial dosage of pralatrexate the patient manifested decrease of the symptoms, by the end of the first cycle the improvement was observed in approximately 20% of body surface area. The adverse reactions presented were fatigue, paresthesia at the site of administration and nausea, all of them were mild and not required additional treatment. Currently the patient has completed 3 cycles of pralatrexate showing improvement of cutaneous involvement in 35% of body surface area.
Discussion
None of the current therapeutic options available for patients with PCL are curative. Many patients are treated sequentially and suffer from frequent morbidity because of the burden of their disease and the cumulative toxicity of therapy3.
Published papers have identified an effective PCL dosing regimen for pralatrexate with a safety profile that is acceptable for continuous long-term use4. In this case this regimen was adapted to the patient and it represents the first experience in Mexico using pralatrexate for Mycosis fungoides. The patient has shown favorable and rapid response to therapy, diminishing symptoms and disease activity. Pralatrexate appears to be a promising agent for the treatment of patients with refractory MF. Yamashita T, Abbade LP, Marques ME, Marques SA. Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update. An Bras Dermatol 2012; 87: 817-28Prince HM, Whittaker S, Hoppe RT. How I treat mycosis fungoides and Sézary syndrome. Blood 2009; 114: 4337-53Al Hothali GI. Review of the treatment of mycosis fungoides and Sézary syndrome: A stage-based approach. Int J Health Sci (Qassim) 2013; 7: 220-39Horwitz SM, Kim YH, Foss F, Zain JM, Myskowski PL, Lechowicz MJ, et al. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 2012; 119: 4115-22

Disclosures
Lopez: Mundipharma: Other: Subsidies for the costs of travel to the ASH annual meeting. Off Label Use: Pralatrexate is approved at a dose of 30mg/m2. In this case I administer a low dose (15 mg/m2) to improve tolerance and maintain in a long term the treatment..