Treatment of Advanced Folliculotropic Mycosis Fungoides in an Elderly Patient with Systemic NHL
For this elderly male with tumor-stage folliculotropic mycosis fungoides and concurrent systemic non-Hodgkin's lymphoma, treatment should prioritize combined topical and systemic therapy with PUVA plus interferon-alpha or systemic retinoids, along with local radiotherapy for individual tumors, while avoiding aggressive polychemotherapy which does not improve survival and increases infectious complications that are the primary cause of death in advanced disease. 1, 2
Treatment Algorithm for Tumor-Stage Folliculotropic MF
Initial Therapy Approach
Combined modality therapy is preferred over monotherapy for extensive tumor-stage disease, with PUVA combined with interferon-alpha or systemic retinoids (including bexarotene) as the standard approach 1, 2
Local radiotherapy (20-24 Gy) should be added for individual tumors, with low-dose radiotherapy (4-8 Gy) sufficient for palliative treatment of specific lesions 1
Total skin electron beam therapy (TSEBT) at 30-36 Gy can be considered, though lower doses (10-12 Gy) have been employed recently with fewer side effects and opportunity for re-treatment 1
Critical Treatment Principles for Elderly Patients
Aggressive polychemotherapy must be avoided as initial therapy because it does not improve overall survival in tumor-stage disease and causes serious side effects, particularly infections which are the primary cause of death in advanced MF 1, 2
Treatment goals should prioritize quality of life and long-lasting remissions with drugs that can be safely used without long-term toxicity, given that MF patients are mostly of advanced age with many concomitant diseases 1, 2
Most patients with advanced disease die from secondary problems such as infections, which are worsened by cytotoxic drugs 2
Specific Considerations for Folliculotropic Variant
Folliculotropic MF is often poorly responsive to both skin-directed and systemic therapies and has a worse prognosis compared to epidermotropic variants 3
A novel regimen combining interferon-gamma, low-dose isotretinoin, and topical carmustine showed high response rates in refractory folliculotropic MF (stages IB-IIIB) in a pilot study 3
Romidepsin demonstrated 60% objective response rate in patients with folliculotropic disease involvement who had received ≥1 previous systemic therapy 4
Management of Concurrent Systemic NHL
Fitness Assessment
A comprehensive geriatric assessment (CGA) is mandatory to guide treatment choice and categorize the patient as fit, vulnerable, or terminally ill 2
Elderly patients should be categorized into three groups: (1) fit patients who can tolerate full-dose standard therapy, (2) vulnerable patients unfit for full-dose therapy but eligible for alternative therapy, and (3) terminally ill patients who should receive best supportive care only 2
Cardiac assessment (LVEF) is required if curative-intent treatment for the systemic NHL is being considered 2
Treatment Coordination
The presence of systemic NHL requires careful coordination between skin-directed therapies for MF and systemic treatment for NHL, with consideration of overlapping toxicities 2
For fit elderly patients <80 years old with systemic NHL, R-CHOP remains the recommended first-line treatment, though this must be balanced against the need to avoid aggressive chemotherapy for the MF component 2
For patients >80 years old or those with significant comorbidities, dose-attenuated R-CHOP may be appropriate for the systemic NHL component 2
Second-Line Options for Refractory Disease
If skin-directed and combination therapies fail, romidepsin (histone deacetylase inhibitor) should be considered given its demonstrated efficacy in folliculotropic MF 4, 1
Gemcitabine may be considered for refractory disease, though responses are generally short-lived 1
Liposomal doxorubicin is an alternative single-agent option for advanced refractory disease 1
For highly selected, relatively young patients with refractory progressive MF, allogeneic stem cell transplantation should be considered, though optimal conditioning and timing remain unknown 1, 5
Critical Pitfalls to Avoid
Earlier therapeutic interventions may aggravate late-stage problems, as radiotherapy or phototherapy may contribute to mutations that increase tumor cell proliferative capacity 2
Multiagent chemotherapy is only justified for stage IV disease with effaced lymph nodes or visceral involvement, or widespread tumor-stage MF that cannot be controlled with skin-targeted and immunomodulating therapies 2
The addition of TSEBT combined with chemotherapy resulted in higher response rates but serious side effects and no difference in overall survival 2