Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial
Cutaneous T-cell lymphoma (CTCL) is a rare and challenging form of non-Hodgkin lymphoma that primarily affects the skin. The MAVORIC trial compared the efficacy and safety of mogamulizumab, a monoclonal antibody targeting CCR4, with vorinostat, an HDAC inhibitor, in patients with previously treated CTCL. This presentation explores the trial design, key findings, and clinical implications, offering insights into advanced treatment options for this complex disease.
Secondary endpoints: Overall response rate (ORR) and overall survival (OS)
Patient Population
372 patients randomized 1:1 to mogamulizumab or vorinostat
Median age: 66 years, with a balanced distribution of disease subtypes
Prior systemic therapies included chemotherapy, retinoids, and other targeted agents
Stratification factors: Disease subtype, prior systemic therapies, and geographic region
Treatment Regimens
Mogamulizumab: 1.0 mg/kg intravenously weekly for 4 weeks, then every 2 weeks
Vorinostat: 400 mg orally daily
Treatment continued until disease progression or unacceptable toxicity
Cross-over to mogamulizumab allowed for vorinostat-treated patients
Key Findings: Progression-Free Survival
Median PFS significantly longer with mogamulizumab (7.7 months vs. 3.1 months)
Hazard ratio for PFS: 0.53 (95% CI: 0.41–0.69, p < 0.0001)
Superiority maintained across all predefined subgroups
Overall Response Rate
ORR higher with mogamulizumab (28% vs. 5% for vorinostat)
Complete response rate: 7% vs. 0%
Response duration longer with mogamulizumab (median 17.6 months vs. 10.4 months)
Safety and Tolerability
Common adverse events with mogamulizumab: Rash, infusion reactions, and lymphopenia
Vorinostat-associated toxicities: Fatigue, nausea, and thrombocytopenia
Serious adverse events more frequent with mogamulizumab (28% vs. 15%)
Overall Survival
Median OS not reached for mogamulizumab vs. 20.4 months for vorinostat
Hazard ratio for OS: 0.64 (95% CI: 0.46–0.90, p = 0.0098)
Long-term follow-up ongoing to assess durability of survival benefit
Clinical Implications
Mogamulizumab demonstrates superior efficacy over vorinostat in relapsed/refractory CTCL
Supports its use as a preferred second-line treatment option
Further research needed to optimize patient selection and combination therapies
The MAVORIC trial establishes mogamulizumab as a more effective treatment option than vorinostat for patients with previously treated cutaneous T-cell lymphoma, offering improved progression-free survival and overall response rates. These findings highlight the importance of targeted therapies in managing advanced CTCL and provide clinicians with valuable data to guide treatment decisions. Future research should explore combination strategies and long-term outcomes to further enhance patient care.
