Chlormethine Gel for Patients with Mycosis Fungoides Cutaneous T Cell Lymphoma: A Review of Efficacy and Safety in Clinical Trial and Real-World Settings

Wehkamp, Ulrike; Ardigò, Marco; Papadavid, Evangelia; Querfeld, Christiane; Nikbakht, Neda

doi:10.1007/s12325-022-02219-w

Cited by 13 publications

(9 citation statements)

References 56 publications

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“…For patients with more-advanced or resistant disease, chlormethine gel maintenance can be combined with other treatment options without concerns about drug–drug interactions ( 23 ). Chlormethine gel has a manageable safety profile ( 22 ), which is important for maintenance treatments. AEs that have been observed with chlormethine gel were all skin related ( 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Expert opinions and clinical experiences with chlormethine gel as maintenance treatment for patients with mycosis fungoides

Geskin,

Querfeld,

Hodak

et al. 2024

Front. Med.

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Maintenance treatment can be recommended for patients with mycosis fungoides (MF) whose disease responds to primary treatment. While positive outcomes have been observed in small studies with maintenance therapy, there is a lack of practical guidelines and agreement on when and how maintenance therapy for MF should be approached. In this article, we discuss expert opinions and clinical experiences on the topic of maintenance therapy for patients with MF, with a focus on chlormethine gel. Ideally, patients should have a durable response before initiating maintenance therapy. The definition of and required duration of durable response are topics that are open to debate and currently have no consensus. Chlormethine gel has several attributes that make it suitable for maintenance therapy; it can be easily applied at home, can be combined with other treatment options for maintenance, and has a manageable safety profile. Chlormethine gel as maintenance therapy can be applied at decreasing frequencies after active treatment with chlormethine gel or other therapies until the minimally effective dose is reached. Patients generally tend to adhere well to chlormethine gel maintenance regimens and may remain on treatment for several years. The experiences described here may be useful for clinicians when deciding on maintenance treatment regimens for their patients. Development of guidelines based on clinical trial outcomes will be important to ensure the most effective maintenance treatment strategies are used for patients with MF.

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Section: Discussionmentioning

confidence: 99%

Expert opinions and clinical experiences with chlormethine gel as maintenance treatment for patients with mycosis fungoides

Geskin,

Querfeld,

Hodak

et al. 2024

Front. Med.

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“…The combination of chlormethine gel with topical corticosteroids has been seen in other real-world studies as well, and this appears to be a relatively common strategy ( 21 – 24 ). Topical corticosteroids are also used in clinical practice to reduce the risk for contact dermatitis, which is one of the most common AEs associated with chlormethine gel treatment ( 14 , 25 ). A prospective, randomized, controlled study directly compared treatment with chlormethine gel alone to the combination of chlormethine gel with the topical corticosteroid triamcinolone ( 26 ).…”

Section: Chlormethine Gel Combination Regimensmentioning

confidence: 99%

Chlormethine gel in combination with other therapies for treatment of mycosis fungoides: a review with patient cases

Ardigò,

Nikbakht,

Teoli

et al. 2024

Front. Med.

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Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients treated with chlormethine gel combined with phototherapy (n = 5), retinoids (n = 16), or mogamulizumab (n = 3) are presented. These different combination regimens showed promising results. Most patients had a complete or partial response following treatment and the combinations were well-tolerated over extended treatment periods. Patients receiving chlormethine gel with retinoids had long-term periods of remission, even after treatment discontinuation. Durations of response of up to 3 years were observed in these patients. This long-term disease control may be the result of disease-modifying effects of chlormethine. Previous studies have shown targeted reductions in malignant T-cell clones in patients treated with chlormethine gel as well as improved post-treatment responses. Further research is needed to determine the effectiveness and safety of combination treatment regimens with chlormethine gel and to assess the impact chlormethine gel has on disease control.

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“…50 The concentration of CL required to induce its clinical effects in the dermal layer has yet to be established. However, since MF plaques have been shown to respond well to topical CL treatment, 25,44,52 it is possible that the minimal amounts of CL shown to reach the dermis in IVPT experiments may be sufficient to exert an effect, potentially by inducing cytotoxic inflammation, with cytokine or chemokine release from an associated influx of reactive T cells.…”

Section: In Vitro Evidencementioning

confidence: 99%

“…[68][69][70] Dermatitis can occur after CL gel treatment and should be managed according to its severity. 52,60 If treatment with CL gel results in a skin reaction, physicians should consider pausing treatment. In patients with mild to moderate dermatitis, treatment with CL gel may be continued at a reduced frequency and in combination with emollients or topical steroids.…”

Section: Dermatitis Avoidance Study (Midas)mentioning

confidence: 99%

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Mechanism of action of chlormethine gel in mycosis fungoides

Guenova

Ortiz‐Romero

Poligone³

et al. 2023

Acad Dermatol Venereol

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Mycosis fungoides (MF), the most common type of cutaneous T‐cell lymphoma, is characterized by proliferation of malignant skin‐tropic T cells. Progression from early‐stage disease (skin patches and/or plaques) to more advanced stages (cutaneous tumours, erythroderma or extracutaneous involvement) occurs slowly and can be discontinuous. Prognosis is poor for the ~25% of patients who progress to advanced disease. Patients at any stage of MF may experience reduced health‐related quality of life (QoL) via a spectrum of physically and psychologically debilitating symptoms that can impact many aspects of daily life. Allogeneic stem‐cell transplantation is a curative treatment option for some patients with advanced disease, but otherwise there is currently no cure for MF; patients are often refractory to several treatments and require lifelong management. The goals of therapy are symptom control, prevention of disease progression, avoidance of treatment‐related toxicity and maintenance/improvement of QoL. Although treatment regimens exist it can be difficult to know how to prioritize them, hence therapies are tailored according to patient needs and drug availabilities, following clinical recommendations. International consensus guidelines recommend skin‐directed therapies (SDTs) as first‐line treatment for early‐stage disease, and SDTs combined with systemic therapy for advanced stages. Chlormethine (CL), also known as mechlorethamine, chlorethazine, mustine, HN2, caryolysine and embichin, is a synthetic deoxyribonucleic acid‐alkylating agent that was used as a chemical weapon (mustard gas) during the First World War. Subsequent investigation revealed that survivors of mustard gas exposure had lymphocytopenia, and that CL could inhibit rapidly proliferating malignant T cells. CL has since been developed as a topical treatment for MF and prescribed as such for over 70 years. This review aims to summarize the current knowledge regarding the mechanism of action of CL in the cutaneous micro‐environment, in the specific context of MF treatment.

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Chlormethine Gel for Patients with Mycosis Fungoides Cutaneous T Cell Lymphoma: A Review of Efficacy and Safety in Clinical Trial and Real-World Settings

Cited by 13 publications

References 56 publications

Expert opinions and clinical experiences with chlormethine gel as maintenance treatment for patients with mycosis fungoides

Expert opinions and clinical experiences with chlormethine gel as maintenance treatment for patients with mycosis fungoides

Chlormethine gel in combination with other therapies for treatment of mycosis fungoides: a review with patient cases

Mechanism of action of chlormethine gel in mycosis fungoides

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