Dimethyl fumarate (DMF) was effective in the treatment of relapsed and refractory (R/R) cutaneous T-cell lymphoma (CTCL), according to findings from a multicenter phase II study published in Blood.
“DMF is a promising new therapeutic approach, especially for combination therapy, as no cumulative toxicities are expected,” said author Jan Nicolay, MD, MSc, of University Medical Center Mannheim in Germany.
Mycosis fungoides (MF) and Sézary syndrome (SS), the most common types of CTCL, have high progression and relapse rates, even after therapies that are very effective initially. There are no curative therapies aside from allogeneic hematopoietic cell transplantation. This lack of options decreases overall survival and increases disease burden, especially in advanced MF and SS. Patients’ quality of life is limited, and they often have challenging symptoms of pruritus and pain.
New targeted therapies have been limited by side effects and short response durations.
The trial was performed at six centers in Germany and enrolled 25 patients with R/R MF or SS who had received at least one topical or systemic pretreatment. Participants were an average of 64 years old, and 12 had stage IV disease. Eight patients had a Modified Severity-Weighted Assessment Tool (mSWAT) score of more than 100 at baseline, with five of these patients having an mSWAT score over 150.
Patients received DMF starting at 30 mg per day, and the dose was escalated weekly by 30 mg per day up to 120 mg per day. After that, DMF was escalated by 120 mg per week up to 720 mg per week or to the highest dose tolerated if a patient had clinically relevant side effects.
Researchers’ analysis showed that six patients had a decrease in mSWAT score of at least 30% after 24 weeks, which was the trial’s primary endpoint, and five patients showed a decrease in mSWAT of at least 50%.
The median dose in the 22 per-protocol patients was 402.4 mg per day. Among those patients, the best overall response rate in the skin was 30.4%, with one complete global response, researchers reported. Four of eight patients with an mSWAT score of at least 100 showed a response in the skin, with one complete response and three partial responses.
Of the five patients who had SS with a high tumor burden in the blood and skin – B2 blood involvement and an mSWAT score of at least 100 – four showed a reduction of more than 50% in mSWAT as their best response. “Skin was the compartment with most and deepest responses,” researchers noted.
The median progression-free survival time was 23 weeks.
Researchers saw no relevant change in quality of life or pain scores, but pruritus decreased from an average of three points out of 10 to 2.17 after treatment and to 2.36 at follow-up. “The study medication could relieve pruritus in several patients with CTCL, which is often one of the most vexing symptoms,” the researchers stated.
Dr. Nicolay noted the tolerability of DMF, with just 17% of patients experiencing severe adverse events. “Therefore, DMF is a promising new therapeutic approach, especially for combination therapy, as no cumulative toxicities are expected.”
Any conflicts of interest declared by the authors can be found in the original article.
Nicolay JP, Melchers S. Albrecht JD, et al. Dimethyl fumarate treatment in relapsed and refractory cutaneous T cell lymphoma - a multicenter phase II study [published online ahead of print, 2023 May 22]. Blood. doi: 10.1182/blood.2022018669.