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

December 2015 | Volume 14 | Issue 12 | Features | 1381 | Copyright © December 2015


Kristen Lo Sicco MD and Jo-Ann Latkowski MD

a maximum of 6 cycles.10 In this study, temozolomide was used either in combination with whole-brain radiation or after treatment with a methotrexate-containing chemotherapy schedule and produced overall survival rates between 10-33 months.10 The most common reported side effects of temozolomide include constitutional symptoms, gastrointestinal symptoms, and hematologic toxicities.12
Romidepsin
Romidepsin is a specific histone deacetylase (HDAC) inhibitor agent derived from the gram negative bacterium, Chromobacterium violaceum.13,14 Through a combination of multiple mechanisms, HDAC inhibitors result in transcription of genes involved in apoptosis and inhibition of tumor growth.13 Two independent Phase II trials demonstrated the benefit of romidepsin for the treatment of refractory CTCL, with an overall response rate of 34% and a 6% complete response rate.13 The US FDA - approved dosing schedule is 14 mg/m2 given intravenously over 4 hours on days 1,8, and 15 of a 28-day cycle.13 With lower rates of neutropenia, the HDAC inhibitors such as romidepsin have less immunosuppressive side effects compared to other systemic chemotherapies used to treat advanced- stage CTCL.14 The most common reported side effects include nausea, vomiting, fatigue, anorexia, and dysgeusia.13 Thrombocytopenia may also occur however this is rapidly reversed after medication discontinuation.14 Although rare, cardiac arrhythmias have been reported including QTc prolongation and for this reason, potassium and magnesium levels should be repleted if necessary to ensure normal levels prior to initiation of romidepsin therapy.14 Also of note, romidepsin deems oral contraception ineffective as it competes with the estrogen receptor.14
Belinostat
Belinostat is a pan-HDAC inhibitor with a mechanism similar to that of romidepsin.15 In a recent phase II trial in patients with relapsed or refractory peripheral or cutaneous T- cell lymphoma, belinostat caused a complete response in 3/29 patients and a partial response in 1/29 patients.15 Additionally, improvement of pruritus was noted in 7/15 patients with significant pruritus at baseline.15 Belinostat was given intravenously at 1,000mg/m2 over 30 minutes on days 1-5 of a 21-day cycle.15 The most common side effects include nausea, vomiting, infusion site pain, and dizziness.15 Serious medication-related side effects were reported in 8/29 CTCL patients and include jugular vein thrombosis, thrombocytopenia, ventricular fibrillation, pneumonitis, ileus, peripheral edema, and apraxia.15

Conclusion

There are several new topical and systemic therapies for the treatment of MF. Topical mechlorethamine gel is FDA approved for the treatment of stage IA and IB MF and may be used as initial therapy or in combination with other skin-directed or systemic therapies. Topical imiquimod and resiquimod have been helpful in early stage MF however larger controlled studies are necessary to determine their efficacy. Temozolomide, Romidepsin, and Belinostat are systemic therapies that may be used to treat recalcitrant or advanced MF.

Disclosure

The authors have no conflicts of interest to declare.

Acknowledgments

Dr. Kristen Lo Sicco is supported by The Louis and Rachel Rudin Foundation Medical Dermatology Fellowship.

REFERENCES

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AUTHOR CORRESPONDENCE

Jo-Ann Latkowski MDJo-Ann.Latkowski@nyumc.org
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