Effectiveness and safety of methotrexate in the treatment of mycosis fungoides: Real‐world data from a multicentre study

Background Methotrexate (MTX) has been a longstanding therapeutic option for mycosis fungoides (MF); however, data on its real‐world effectiveness remain limited. Objectives To evaluate treatment‐related outcomes of oral MTX in patients with early‐ and late‐stage MF. Methods This is a retrospective multicentre analysis involving MF subjects from five referral centres for cutaneous lymphomas in Greece. Data regarding the effectiveness and safety were analysed. Results In total, 211 MF patients were enrolled (males, 68.3%) with a median (IQR) age of diagnosis at 68.3 (56–75) years. Late‐stage (IIB‐IVB) disease was present in 124 patients (59.3%). MTX monotherapy was administered to 112 (53.1%) patients, with 99 receiving combination regimens with phototherapy, interferon and retinoids. MTX was used as first‐line regimen in 103 (48.9%) cases. An overall response rate (ORR) of 55.5% was observed with 29.9% of patients achieving complete responses. MTX demonstrated greater effectiveness as a first‐line treatment compared to subsequent use with no significant differences between monotherapy and combination therapy. The median time to best response was 3.8 months (IQR 2.3–9.9 months). Patients with erythrodermic disease (Stage III) had better ORRs compared to patients with tumour stage disease (Stage II) (61.1% vs. 44.8% respectively). The progression‐free survival (PFS) varied according to stage, with a median PFS of 17.1 months for early‐stage disease, 5.7 months for Stage IIB disease, 46 months for Stage III and 9.6 months for Stage IV disease (0.7‐.). Serious adverse (Grade 3) events leading to treatment discontinuation occurred in 14 (6.7%) cases. All patients received oral MTX once weekly with a median weekly dose of 15 mg/week (7.5–25). Conclusion Our findings support MTX as a viable treatment option for MF, particularly when used in the first‐line setting, offering a favourable benefit/risk profile. Response rates are stage‐dependent, with erythrodermic patients achieving superior and durable responses.