French real-life retrospective study in patients with mycosis fungoides and Sezary syndrome treated by mogamulizumab

Background: Mogamulizumab is a defucosylated monoclonal antibody targeting the C-C chemokine receptor 4 (CCR4) and approved for the treatment of adult patients with mycosis fungoides (MF) and Sezary syndrome (SS) who have received at least one prior systemic therapy. The efficacy of mogamulizumab was demonstrated in the open-label, phase 3 MAVORIC clinical trial comparing mogamulizumab to vorinostat. This retrospective observational study was conducted in 14 French centres to further assess efficacy and safety of mogamulizumab in a real-life setting. Methods: Data collected from medical records of MF and SS patients treated with mogamulizumab between February 2014 and March 2020 in the participating centres were analysed. Patients treated with mogamulizumab in the MAVORIC trial and still alive at the end of the trial were also included (n=20 pts). The primary endpoint was efficacy based on the percentage of patients achieving complete (CR) or partial (PR) response according to the Global Response Score for MF/SS, at mogamulizumab best response (overall response - ORR). Safety was also evaluated on the number and type of adverse events. Results: A total of 124 patients aged 69.3±11.8 (mean ± standard deviation [SD]) years, treated with mogamulizumab were included. Patients (MF: n=55, SS: n=69) had an average disease duration of 4.8±3.4 and 2.8±3.1 (mean ± SD) years, respectively. Prior to mogamulizumab, patients had received a median of 3 systemic treatments lines. The stage of the disease at mogamulizumab initiation was IA – 1.7%; IB – 13.4%; IIA – 6.7%; IIB – 5.9%; IIIA – 6.7%; IIIB 7.6%; IVA1 – 49.6%; IVA2 – 6.7%; IVB – 1.7%. 81 patients had blood involvement at mogamulizumab initiation (B1: n=16; B2: n=65). The average duration of treatment with mogamulizumab was 7.6±11.6 (mean ± SD) months. The ORR was 58.6% [95% CI: 48.8–67.8] in the total population vs 47.1% [95% CI: 32.9–61.5] and 68.3% [95% CI: 55–79.7] in MF and SS subsets, respectively. The response in the blood compartment was 55% [95% CI: 45.2–64.4] in the total population vs 71.7% [95% CI: 58.6–82.5] in SS patients. Side effects related to treatment were recorded in 54% of the patients. Skin adverse reactions were the most common adverse events, with 45 recorded instances occurring in 26 patients; over half (55.6%) of all instances were mild-to-moderate in severity. Infusion-related reactions were recorded in 12.1% of patients and were limited to the first (88%) or second (12%) infusion; only 3 patients had a Grade 3 reaction, but none led to treatment discontinuation. Overall, 7 patients passed away, 5 owing to disease progression (1 stage IIB, 3 stage IVA1, 1 stage IVA2) and 2 to sepsis; neither case of sepsis was considered treatment related. Conclusion: This real-life- survey shows both a significant ORR and a favourable safety profile in MF and SS patients treated with mogamulizumab. The shown data are consistent with those observed in MAVORIC study.