Gabriele Roccuzzo, Paolo Fava, Serena Rupoli, Erika Morsia, Miriam Teoli, Pier Luigi Zinzani, Alessandro Pileri, Alessandra Tucci, Silvia Alberti Violetti, Cesare Massone, Adalberto Ibatici, Andrea Bernardelli, Corrado Imbriani, Sonya De Lorenzo, Patrizia Bernuzzi, Nicola Pimpinelli, Marco Paulli, Francesco Onida, Maria Cantonetti, Giacomo Loseto, Raffaele Filotico, Maria Pina Simula, Amalia Figuera, Mauro Alaibac, Renato Zambello, Chiara Cavalloni, Alberto Fabbri, Giorgio Priolo, Luigi Marcheselli, Pietro Quaglino
This large real-world study confirms the effectiveness of mogamulizumab and identifies ORR4 as a robust on-treatment prognostic marker independently associated with OS, PFS and TTNT. These findings support the incorporation of ORR4 as a clinically meaningful endpoint in real-world studies and routine management of MF/SS.
BACKGROUND: Conventional response endpoints do not adequately capture durable clinical benefit in mycosis fungoides (MF) and Sézary syndrome (SS). Overall response lasting ≥ 4 months (ORR4) has been proposed as a clinically meaningful endpoint in clinical trials, but its prognostic value in real-world mogamulizumab-treated patients remains unknown.
OBJECTIVES: To evaluate the effectiveness and safety of mogamulizumab in routine clinical practice and investigate the prognostic relevance of ORR4 in patients with MF/SS.
METHODS: FIL-MOGA was a nationwide, multicenter, retrospective study including 98 patients with MF/SS treated with mogamulizumab between January 2021 and December 2023 across 18 centers of the Italian Lymphoma Foundation (FIL). The primary endpoint was ORR4. Survival outcomes were assessed using Kaplan-Meier estimates, 4-month landmark analyses, and Cox proportional hazards models treating ORR4 as a time-varying covariate (TVC).
RESULTS: After a median follow-up of 35 months, ORR4 was achieved in 44 of 93 (47.3%) evaluable patients. Best overall response increased from 29.4% at 1 month to 38.0% at 4 months and 58.1% during follow-up. ORR4 varied significantly according to baseline disease stage (p=0.022), ranging from 10.0% in stage IIB to 70.8% in stage IVA1 disease. In landmark analyses, ORR4 was associated with improved 24-month OS (76% vs 60%; p=0.006), PFS (58% vs 35%; p=0.001), and TTNT (76% vs 47%; p=0.002). These findings were confirmed in time-dependent analyses (OS HR 2.53, p=0.008; PFS HR 2.70, p=0.001; TTNT HR 3.04, p=0.003). In multivariable models, lack of ORR4 remained independently associated with worse OS (HR 3.18, p=0.002), PFS (HR 2.67, p=0.002), and earlier initiation of subsequent systemic therapy (HR 4.27, p=0.001). Skin adverse events were associated with higher ORR4 rates (70% vs 40%, p=0.017) but not independently with survival outcomes. Thirteen patients (13%) underwent allogeneic hematopoietic stem cell transplantation after mogamulizumab.
CONCLUSIONS: This large real-world study confirms the effectiveness of mogamulizumab and identifies ORR4 as a robust on-treatment prognostic marker independently associated with OS, PFS and TTNT. These findings support the incorporation of ORR4 as a clinically meaningful endpoint in real-world studies and routine management of MF/SS.