Newer Treatment Options for Mycosis Fungoides
For advanced mycosis fungoides, brentuximab vedotin and mogamulizumab represent the most significant recent therapeutic advances, with brentuximab showing particularly high response rates in CD30-expressing disease and mogamulizumab demonstrating effectiveness in patients with blood involvement. 1, 2
Novel Monoclonal Antibodies (Most Recent Advances)
Brentuximab Vedotin
- This antibody-drug conjugate targeting CD30 is administered intravenously at 1.8 mg/kg every 21 days for up to 16 cycles, and shows the best responses when tumor cells express ≥10% CD30. 3, 1
- Response rates are encouragingly high in phase II trials, with tumor responses correlating directly with the proportion of CD30-expressing cells. 3
- Approved in 2017 specifically for relapsed mycosis fungoides/Sézary syndrome. 2
Mogamulizumab
- This anti-CCR4 antibody is particularly effective for cases with blood involvement, achieving high response rates in patients with erythrodermic disease. 1
- Approved in 2018 for relapsed disease and represents a major advance for patients with leukemic involvement. 2
Established Systemic Therapies with Proven Success
Bexarotene (Retinoid X Receptor Agonist)
- For early-stage disease (IA/IB/IIA), bexarotene achieves 54% response rates at 300 mg/m² daily, while advanced disease (IIB-IVB) shows 45% response rates with notable pruritus reduction. 3
- Licensed in Europe for advanced stages (IIB-IVB) refractory to at least one systemic agent. 3
- Maximum responses may require 6 months of treatment, and therapy should continue until loss of response. 3
- Common pitfall: Most patients require concurrent treatment for hyperlipidemia and central hypothyroidism while on therapy. 3
- Side effects are generally mild and transient but metabolic monitoring is essential. 3
Alemtuzumab (Anti-CD52)
- Phase II trials show high overall response and complete remission rates in advanced disease, with dramatic symptomatic benefit particularly in Sézary syndrome, though responses are typically short-lived (minority achieve >12 months). 3
- Most effective in erythrodermic stage III-IVA1 disease but ineffective in patients with tumors and large cell transformation. 3
- Standard dosing is 30 mg intravenously three times weekly, though subcutaneous 10 mg three times weekly shows similar efficacy with reduced toxicity. 3
- Critical caveat: Cytomegalovirus reactivation remains a significant concern, and patients require irradiated blood products. 3
Skin-Directed Therapies for Early Disease
Phototherapy
- PUVA achieves 79-88% response rates in stage IA and 52-59% in stage IB disease. 4
- Combining PUVA with interferon reduces cumulative UVA dose and prolongs response duration compared to PUVA alone. 3
- Narrow-band UVB is appropriate only for patches or very thin plaques. 4
Radiotherapy
- Local radiotherapy can be curative in early localized disease and pagetoid reticulosis using 2-3 fractions of low-energy (80-120 kV) superficial radiation. 4
- For patients developing one or few tumors (stage IIB), additional local radiotherapy often suffices. 4
Extracorporeal Photopheresis (ECP)
- ECP demonstrates 35-71% overall response rates in erythrodermic disease (stage III/IVA), making it a preferred option for erythrodermic patients where chemotherapy responses are generally poor. 4
- FDA-licensed for CTCL treatment, though randomized studies on overall survival impact are lacking. 3
Important Treatment Principles
What NOT to Do
- Avoid cyclosporine in mycosis fungoides as it may cause rapid disease progression despite relieving pruritus. 3
- Early aggressive chemotherapy with radiation does not improve survival and causes considerable side effects. 4
- Autologous stem cell transplantation has shown disappointing results. 4
Chemotherapy Considerations
- Mycosis fungoides is relatively chemoresistant with short-lived responses; reserve chemotherapy only for effaced lymph nodes, visceral involvement (stage IV), or widespread tumor-stage disease uncontrolled by other therapies. 4
- Single-agent options include gemcitabine and liposomal doxorubicin. 4
- Multi-agent regimens achieve approximately 30% complete responses but these are short-lived (median 3-41 months). 4
Potential Curative Option
- Allogeneic hematopoietic stem cell transplantation is the only treatment offering potential cure with durable complete remission, and should be considered in young patients with refractory, progressive disease and markedly short life expectancy. 4, 1
- Associated mortality is significant, but graft-versus-lymphoma effect may be therapeutically important. 3
Emerging Cellular Therapies
- Various cellular therapies are under investigation in advanced-phase clinical trials, representing further attempts to expand treatment options. 2