The pregnant pause in cutaneous lymphoma

By Jennifer Villasenor-Park, MD, FAAD
Oct. 2, 2024
Vol. 6, No. 40

I first met Anne when she was 30 years old and was experiencing a significant flare of her mycosis fungoides. She had already lived with the disease for 18 years having been diagnosed at the age of 12 having experienced several treatments including phototherapy, methotrexate, and interferon. She understood the chronic nature of her disease and the possibility of progression. Despite this knowledge, she, like many women her age, desired children and was plagued by the worry of possible harm to her unborn child because of her CTCL or the treatment she might receive if the disease progressed during pregnancy. As her physician, I was asked to provide pregnancy-safe treatment options but struggled with the paucity of referenced data available to offer her.

Primary cutaneous lymphomas are a rare heterogenous group of non-Hodgkins lymphomas of which mycosis fungoides (MF) is the most common variant. While most patients are diagnosed between the ages of 55-60, a small percentage of patients are diagnosed at a younger age. (1,2) Diagnosing and treating female patients during their childbearing years presents unique challenges given the rarity of pregnancy-associated CTCL and limited options for pregnancy-safe treatment. Moreover, it is not clear whether the relatively immunosuppressive environment of the pregnant patient promotes progression of disease.

Few data exist regarding prognosis in pregnancy associated-CTCL and its effect on pregnancy and fetal outcomes. Most published data come from small case series and case reports. (3-7) The majority of patients in these studies had early stage disease (stage IA-IIA) at the time of diagnosis and during pregnancy. Most patients did not have progression of their disease during pregnancy and the postpartum period. (3,4) However, a few studies described patients with both early and advanced stage disease who developed flares during pregnancy that were attributed to treatment discontinuation and the immunosuppressive effects of pregnancy. (4-8)

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One report described a patient with stage IIIA (erythrodermic) CTCL who was treated with PUVA and interferon, but discontinued all treatment once she became pregnant. One week following delivery, she presented with erythroderma with lymphadenopathy and biopsies demonstrating CD30+ large cell transformation, a histologic feature that is associated with progression of disease. (8) Additionally, Guitart et al described a patient with stable stage IA disease who rapidly progressed to stage IB disease following discontinuation of interferon alpha-2b during her pregnancy. During her second pregnancy, she continued her interferon alpha-2b therapy and had adequate disease control requiring radiation therapy following delivery to treat new plaques that she developed during pregnancy. (5) It is clear that additional studies are necessary to determine whether the immunosuppressive effects of pregnancy play a significant role in modulating disease in patients with CTCL.

Treatment of CTCL is dictated by stage of disease with the goal of using therapies with the least toxicity. In the non-gravid patient, skin-directed therapy (e.g., phototherapy, topical nitrogen mustard, topical carmustine, topical imiquimod, topical bexarotene or other retinoids) is first-line treatment in early-stage patients. (9) While there are no guidelines for pregnancy-safe treatment options specific for CTCL, there are acceptable skin-directed treatments for pregnant patients including topical steroids and phototherapy. (10)

For more advanced disease or patients failing skin-directed treatment, systemic therapy with oral retinoids (e.g, bexarotene, isotretinoin), interferons, methotrexate, other IV systemic treatments (e.g., mogamulizumab, romidepsin, pralatrexate, brentuximab), and radiation are considered in the non-gravid patient. While most of these therapies are contraindicated in pregnancy or in those considering pregnancy, use of interferon during pregnancy has been described. (5,11) In patients with reproductive potential in whom systemic treatment is being considered, pregnancy testing should be performed and fertility preservation should be discussed. A multi-disciplinary approach with collaboration between dermatology, oncology, neonatology, and obstetrics is important during all stages of disease to ensure treatment optimizes both maternal and fetal outcomes. Timing of treatment is also critically important. Multicenter retrospective studies in the oncology literature indicate that treatment with systemic chemotherapy can have acceptable maternal and fetal outcomes when given after the first trimester. (12)

When Anne finally became pregnant, she had no clinical evidence of disease following many months of treatment with interferon, topical steroids, and phototherapy. She discontinued phototherapy during her first trimester and has opted to stay off treatment. She remains free of disease during her second trimester and plans to re-start phototherapy if her disease flares.

Given the available data, it may be helpful to inform our patients that treatment with topical steroids, phototherapy, and/or interferon during the second and third trimesters are relatively safe treatment options and can be helpful to prevent disease flares and progression of disease during pregnancy and in the postpartum period. Clearly, additional studies to define prognosis and identify pregnancy-safe treatment options are needed to prevent a pause in treatment as well as the potential progression of disease.

In conclusion, 1) It is essential to have a multi-disciplinary team involved in the care of patients with pregnancy-associated cutaneous lymphoma to develop goals-of-care that balance maternal and fetal well-being; 2) Fertility preservation should be discussed following diagnosis; 3) Timing of treatment is important in patients with pregnancy associated CTCL and continuing treatment during the second and third trimesters should be considered to prevent disease flares/progression; 4) Additional studies are needed to determine the association between pregnancy and CTCL and to establish guidelines for pregnancy-safe treatment.

Point to Remember: Cutaneous T-cell lymphoma during pregnancy presents unique challenges in preventing disease progression and maintaining fetal viability. Many standard therapies used in the non-gravid state are contraindicated; topical steroids, phototherapy, and interferon are considered safe options. A multidisciplinary approach is necessary for optimal management.

Our expert’s viewpoint

Danielle DeHoratius, MD, FAAD

Pregnancy can bring on many cutaneous conditions. Melasma, linea nigra, varicose veins, and striae gravidarum are common examples. Most of them are inconsequential and reminders that the body is undergoing tremendous changes to nourish this growing life. Many of them also tend to improve or resolve once the pregnancy is complete and the baby is born. Unfortunately, there are a handful of diseases attributable to pregnancy that can worsen during the course of the pregnancy, such as pruritic folliculitis of pregnancy, pemphigoid gestationis, prurigo of pregnancy, and intrahepatic cholestasis, to name a few. Pregnancy can certainly be anxiety provoking as can having cutaneous T-cell lymphoma. The combination of the two along with the potential for worsening CTCL secondary to pregnancy can make patients even more apprehensive.

Having trained with some of the CTCL greats, Drs. Edelson, Heald, and Girardi, I learned that they would often reassure the patients with early-stage disease that they have a normal life expectancy. This changes with more advanced disease and it also includes disease progression. Dr. Villasenor-Park beautifully describes the essential need for more research on both treatment and potential evolution of disease. Knowledge is power and we need to provide these patients with more understanding of what could lie ahead.

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12. Pinnix CC, Osborne EM, Chihara D, et al. Maternal and Fetal Outcomes After Therapy for Hodgkin or Non-Hodgkin Lymphoma Diagnosed During Pregnancy. JAMA Oncol 2016; 2(8): 1065-9.

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