• Efficacy and safety of mogamulizumab by patient blood classification

      Scarisbrick, J.; Zinzani, P. L.; Cowan, Richard A; Nicolay, J. P.; Caballero, D.; Sokol, L.; Pinter-Brown, L; Rosen, J. P.; University Hospital Birmingham, Birmingham, (2021)
      Cutaneous T-cell lymphomas (CTCLs) are rare, serious and potentially life-threatening forms of non-Hodgkin lymphoma that primarily present in skin. Mycosis fungoides (MF) and S ezary syndrome (SS) are the classic subtypes and together account for around two-thirds of all CTCLs. Initial methods of disease staging in MF and SS built upon the tumour-node-metastasis (TNM) classification using disease-specific findings. Blood classification (B0–2) was added to staging in 2007 based upon the recognition of blood involvement as a prognostic factor; increasing blood tumour burden has previously been linked with worsening of overall survival (OS) and disease-specific survival (DSS), and an increased risk of disease progression (RDP) (Agar 2010, Am Soc J Clin Oncol), although this is a subject of debate and further study. Patients with B1 disease have previously been shown to have a median survival of just 3.2 years, similar to B2 for which it was 3.1 years (Agar 2010, Am Soc J Clin Oncol). The addition of blood classification allows for more specific disease staging which may inform clinical management strategy, whilst also contributing to a better understanding of prognostic factors and treatment response in MF and SS. This post hoc analysis from the MAVORIC trial examined the efficacy and safety of mogamulizumab (MOGA) compared with vorinostat (VORI), stratified by patient blood classification. Materials & Methods: MAVORIC (NCT01728805) was an openlabel, phase 3 study where patients were randomized 1:1 to receive either intravenous MOGA 1.0 mg/kg weekly for the first 28 day cycle, then on days 1 and 15 of subsequent cycles, or oral VORI 400 mg once daily. VORI patients who experienced disease progression or intolerable toxicity could cross over to MOGA. The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In MAVORIC, investigator-assessed PFS was significantly longer for MOGA than VORI overall at 7.7 months and 3.1 months, respectively (P < 0.0001). When data were stratified by blood classification, PFS was found to be significantly superior for MOGA as compared to VORI in patients with both B1 and B2 disease (Table 1). Overall response rate (ORR) was also significantly greater for MOGA than VORI in MAVORIC at 28.0% and 4.8%, respectively (P < 0.0001), and was found in this analysis to be significantly greater for MOGA than VORI in those patients with B2 disease (Table 1). ORR for B1 was not significant, but showed a trend (25.8% vs. 6.5% for MOGA and VORI, respectively). Time-to-nexttreatment (TTNT) was not significant for patients without blood involvement (B0), but was significantly greater for MOGA in patients with blood involvement (B1 or B2) with 13.07 and 3.30 months for MOGA and VORI, respectively (P < 0.0001) (Table 1). Drug-related treatment-emergent adverse events (TEAEs) were similar in patients regardless of blood involvement and were lower for MOGA than VORI at each blood classification level (Table 1). Conclusion: MOGA is effective in patients with blood involvement (B1 and B2), often showing a greater clinical benefit in patients in the B1 and B2 groups than those in the B0 group. Drug safety is similar between patients irrespective of level of blood involvement.
    • Quality of life effect of the Anti-CCR4 monoclonal antibody mogamulizumab versus vorinostat in patients with cutaneous t-cell lymphoma

      Porcu, P.; Hudgens, S.; Horwitz, S.; Quaglino, P.; Cowan, Richard A; Geskin, L.; Beylot-Barry, M.; Floden, L.; Bagot, M.; Tsianakas, A.; et al. (2020)
      Background: Sézary syndrome (SS) and mycosis fungoides (MF), 2 types of cutaneous T-cell lymphoma, cause significant morbidity and adversely affect patients' quality of life (QoL). The present study assessed the QoL measurement changes in patients receiving mogamulizumab versus vorinostat. Patients and methods: A multicenter phase III trial was conducted of patients with stage IB-IV MF/SS with ≥ 1 failed systemic therapy. The QoL measures included Skindex-29 and the Functional Assessment of Cancer Therapy-General. The symptoms, function, and QoL subdomains were longitudinally modeled using mixed models with prespecified covariates. Meaningful change thresholds (MCTs) were defined using distribution-based methods. The categorical changes by group over time and the time to clinically meaningful worsening were analyzed. Results: Of the 372 randomized patients, mogamulizumab demonstrated improvement in Skindex-29 symptoms (cycles 3, 5, and 7; P < .05) and functional (cycles 3 and 5; P < .05) scales. A significantly greater proportion of mogamulizumab-treated patients improved by MCTs or more from baseline in the Skindex-29 symptoms domain (cycles 3, 5, 7, and 11) and functioning domain (cycle 5). Significant differences in the Functional Assessment of Cancer Therapy-General physical well-being (cycles 1, 3, and 5; P < .05) were observed in favor of mogamulizumab and a greater proportion of patients had declined by MCTs or more at cycles 1, 3, 5, and 7 with vorinostat treatment. The median time to symptom worsening using Skindex-29 was 27.4 months for mogamulizumab versus 6.6 months for vorinostat. In the patients with SS, the time to worsening favored mogamulizumab (P < .005) for all Skindex-29 domains. The time to worsening was similar for the 2 MF treatment arms. Conclusion: The symptoms, function, and overall QoL of patients with MF/SS favored mogamulizumab over vorinostat across all time points. Patients with the greatest symptom burden and functional impairment derived the most QoL benefit from mogamulizumab.