Randomized Mechlorethamine/Chlormethine Induced Dermatitis Assessment Study (MIDAS) Establishes Benefit of Topical Triamcinolone 0.1% Ointment Cotreatment in Mycosis Fungoides

Abstract

Introduction: Treatment of early-stage mycosis fungoides (MF) requires safe, skin-directed therapies. Medication side effects can lead to underutilization of effective therapies. The objective of this study was to assess the use of topical triamcinolone 0.1% ointment as a means of reducing contact dermatitis associated with topical mechlorethamine/chlormethine gel for the treatment of MF. Methods: This prospective, randomized, openlabel study evaluated 28 adults with mycosis fungoides who were eligible for treatment with topical mechlorethamine/chlormethine gel from December 17, 2017 to December 23, 2020. Patients were treated for 4 months with clinical follow-up through 12 months. Patients had half of their lesions also treated with topical triamcinolone 0.1% ointment (while the other half were treated with mechlorethamine/chlormethine alone). The study was self-controlled with separate lesions in the same patient receiving each treatment arm. Treatment arms were determined by the flip of a coin. Results: Twenty-eight patients enrolled (17 men (61%) and 11 women (39%)). Demographics included 25 White, 2 African Americans, and 1 Asian patient. Twenty-five completed the 12-month follow-up. Triamcinolone 0.1% ointment led to increased tolerability of mechlorethamine/chlormethine gel but did not change the efficacy of mechlorethamine/chlormethine. There was a statistically significant 50% decrease in dermatitis (SCORD score) at month 2 in the triamcinolone-treated arm. Conclusions: Topical triamcinolone ointment is a helpful adjuvant therapy when treating patients with topical mechlorethamine/ chlormethine gel. It diminishes inflammation and does not reduce efficacy. The peak incidence of dermatitis in the study occurred in the second and third months. Trial Registration: ClinicalTrials.gov identifier, NCT03380026.

Mechlorethamine Hydrochloride Gel in the Treatment of Mycosis Fungoides–Type Cutaneous T-Cell Lymphoma (MF-CTCL): A Focus on Patient Selection and Special Considerations

“…In MIDAS, investigators assessed the impact of coadministration of topical triamcinolone ointment 0.1% (TAC) and NM gel on 28 patients with MF. 16 Using TAC in conjunction with NM led to a significant decrease in pruritus and mild-moderate (but not severe) contact dermatitis, particularly at months 2 and 3 of treatment. Importantly, the addition of TAC did not appear to adversely impact the efficacy of NM; in fact there was an improvement noted in the combination treatment group, though this did not reach statistical significance.…”

“… Decrease in mSWAT with treatment correlated with decrease in Skindex-29 (p = 0.026). Alexander-Savino et al (2022) 16 Prospective, randomized, open-label, two-arm, phase II trial N = 28 Stage IA or IB Topical 0.106% NM gel once daily or topical 0.106% NM gel and TAC 0.1% ointment once daily to at least 8cm 2 lesion for 4 months Primary endpoint impact of TAC 0.1% ointment on prevention of NM-associated dermatitis by adapted SCORD. Secondary endpoint comparing efficacy between arms utilizing CAILS.…”

“… 13 Similarly, post hoc analysis of the registrational study of NM gel similarly noted an association between the occurrence of contact dermatitis and response, suggesting that contact dermatitis related to NM gel may also be a predictor of response. 14 In the Mechlorethamine/Chlormethine Induced Dermatitis Assessment Study (MIDAS), 16 the severity of contact dermatitis did not appear to correlate with efficacy of NM therapy, though the number of patients evaluated in the MIDAS study (n = 25) was low compared to the Stanford series (n = 203) and the registrational study (n = 260).…”

“…Importantly, the addition of TAC did not appear to adversely impact the efficacy of NM; in fact there was an improvement noted in the combination treatment group, though this did not reach statistical significance. 16 The product insert for NM gel 17 recommends daily application to affected areas of skin in accordance with the frequency used in the registration trial. 9 In the 2-year observational PROVe study, patterns of use and response of NM gel in a real-world cohort of patients with MF was described.…”

Chlormethine Gel Versus Chlormethine Ointment for Treatment of Patients with Mycosis Fungoides: A Post-Hoc Analysis of Clinical Trial Data

“…Patients who experience allergic contact dermatitis may need to discontinue gel treatment permanently, while those with irritant contact dermatitis can often continue treatment or restart treatment after a brief interruption, depending on the severity of the reaction. The association seen between dermatitis and response highlights the importance of continuing treatment with chlormethine gel with a modified application schedule and/or the addition of topical corticosteroids, which can help patients to remain on treatment [19,25,26].…”