Efficacy and safety of mogamulizumab by patient baseline blood tumour burden: a post hoc analysis of the MAVORIC trial

Abstract

Background: Mogamulizumab was compared with vorinostat in the phase 3 MAVORIC trial (NCT01728805) in 372 patients with relapsed/refractory mycosis fungoides (MF) or Sézary syndrome (SS) who had failed ≥1 prior systemic therapy. Mogamulizumab significantly prolonged progression-free survival (PFS), with a superior objective response rate (ORR) versus vorinostat. Objectives: This post hoc analysis was performed to evaluate the effect of baseline blood tumour burden on patient response to mogamulizumab. Methods: PFS, ORR, time to next treatment (TTNT), skin response (modified Severity-Weighted Assessment Tool [mSWAT]), and safety were assessed in patients stratified by blood classification (B0 [n=126], B1 [n=62], or B2 [n=184], indicating increasing blood involvement). Results: Investigator-assessed PFS was longer for mogamulizumab versus vorinostat across all blood classes; significantly so for B1 and B2 patients. ORR was higher with mogamulizumab than with vorinostat in all blood classification groups, and more markedly so with escalating B-class (B0: 15.6% vs 6.5%, P = 0.0549; B1: 25.8% vs 6.5%, P = 0.2758; B2: 37.4% vs 3.2%, P < 0.0001). TTNT was significantly longer for patients treated with mogamulizumab versus vorinostat with B1 (12.63 vs 3.07 months; HR 0.32 [95% CI 0.16-0.67]; P = 0.0018) and B2 (13.07 vs 3.53 months; HR 0.30 [95% CI 0.21-0.43]; P < 0.0001) blood involvement. In the mogamulizumab arm, 81 patients (43.5%) had ≥50% change in the mSWAT versus 41 patients (22.0%) with vorinostat; mSWAT improvements with mogamulizumab occurred most often in B1 and B2 patients. Rapid, sustained reductions were seen in CD4+ CD26- cell counts and CD4:CD8 ratios in mogamulizumab patients for all B-classes. Treatment-emergent adverse events were less frequent overall with mogamulizumab and similar in frequency regardless of B-class. Conclusions: This post hoc analysis indicates greater clinical benefit with mogamulizumab versus vorinostat in patients with MF and SS classified as having B1 and B2 blood involvement.