Effectiveness of mogamulizumab in patients with Mycosis Fungoides or Sézary syndrome: A multicentre, retrospective, real‐world French study

Abstract

BackgroundEfficacy and safety of mogamulizumab, a monoclonal antibody directed against C‐C chemokine receptor 4, were demonstrated in a previous multinational clinical trial conducted in patients with previously treated cutaneous T‐cell lymphoma (CTCL): Sézary syndrome (SS) or Mycosis Fungoides (MF).ObjectivesThe real‐world French OMEGA study aimed to describe effectiveness and tolerability of mogamulizumab in adult patients with CTCL, overall and according to the disease (SS or MF).MethodsIn this retrospective study, patients treated with mogamulizumab for SS or MF were included from 14 French expert centres. The overall response rate (ORR) under treatment was described (primary criterion), as well as treatment use and safety data.ResultsThe 122 analysed patients (69 SS, 53 MF) were aged 66.6 ± 12.1 years at mogamulizumab initiation, and their median disease duration was 2.5 years (IQR: 1.3–5.6). Prior to treatment start, they received a median of three systemic CTCL therapies (2–5). Overall, 77.8% of patients suffered from advanced disease (Stage IIB–IVB), with frequent blood (B1/B2) involvement (67.5%). Over the treatment period (median: 4.6 months, 2.1–7.2), 96.7% of patients received all the planned mogamulizumab infusions. Among the 109 patients evaluable for effectiveness, ORR was 58.7% (95% CI [48.9–68.1]) overall, 69.5% [56.1–80.8] in SS and 46.0% [31.8–60.7] in MF. Compartmental response in the blood was observed in 81.8% [69.1–90.9] of SS patients. Skin responses were observed in 57.0% [47.0–66.5] of patients overall, 66.7% [52.9–78.6] in SS and 46.0% [31.8–60.7] in MF. The most common serious adverse drug reactions were rash (8.1% of patients) and infusion‐related reactions (2.4%) which led to treatment discontinuation in 7.3% and 0.8% of patients, respectively. One patient with SS died from mogamulizumab‐related tumour lysis syndrome.ConclusionsThis large French study confirmed the effectiveness and tolerability of mogamulizumab in SS and MF patients in routine medical practice.

Mogamulizumab Combined with Extracorporeal Photopheresis as a Novel Therapy in Erythrodermic Cutaneous T-cell Lymphoma

“…Our results suggest that the combination of mogamulizumab and ECP shows superior efficacy in cutaneous involvement compared to approved targeted therapies for MF/SS, including the monotherapy of mogamulizumab and brentuximab vedotin [ 9 , 11 , 28 ]. This observation holds true even when compared to recently published phase I and phase II studies investigating innovative drug candidates such as tenalisib, dimethyl fumarate, or pembrolizumab for CTCL [ 16 , 29 , 30 ].…”

“…All AEs with their respective CTCAE grades are shown in Figure 3 C. All AEs could possibly have been induced or aggravated by the combination treatment. Due to the retrospective character of this study, it was not possible to clarify this in more detail, but all observed AEs except for autoimmunhypophysitis are described for either mogamulizumab or ECP therapy in the literature [ 9 , 11 , 24 , 25 ]. No AE led to treatment discontinuation.…”

“…Real-world data from France assessing the efficacy of mogamulizumab were recently published. An ORR was achieved in the skin of 66.7% of patients with SS and in 46% in patients with MF [ 11 ]. The first study on ECP in patients with CTCL was published in 1987 by Edelson et al; data from this study were reanalyzed in 2012 using the current international criteria and it was found that the ORR in the skin was 74% [ 13 , 14 ].…”

“…However, the number of patients with AE grade ≥ 3 (45.5%) was comparable to treatment with mogamulizumab monotherapy in the phase 3 study MAVORIC (41%) [ 9 ]. The main side effects observed were MAR (45.5%), anemia (27.3%), lymphocytopenia (27.8%), and infusion-related reaction (16.7%), compared to the real-life data, where MAR was described in 14.5% (SS 18.8%), lymphocytopenia in 23.4% (SS 30.4%), and infusion-related reaction 2.1% (SS 15.9%) of cases [ 11 ]. In a meta-analysis comparing 14 studies where mogamulizumab was administered for different types of cancers, the most common AEs in patients receiving mogamulizumab in combination with other drugs were neutropenia (event rate (ER) of 0.812), anemia (ER of 0.687), lymphocytopenia (ER of 0.619), and gastrointestinal disorder (ER of 0.599).…”

“…Notably, the study demonstrated a 68% partial response in the blood following mogamulizumab treatment. Recently, in September 2023, real-world data from France were published [ 11 ], which reported even more promising outcomes, showing an overall response rate (ORR) in the blood of 81.8% through mogamulizumab monotherapy.…”