Background

Cutaneous T-cell lymphomas (CTCL) are rare forms of non-Hodgkin lymphoma, presenting primarily in the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account for around two-thirds of all CTCL cases.

MAVORIC (NCT01728805) was an open-label, phase 3 study comparing mogamulizumab (Moga) to vorinostat (Vori) in MF and SS patients (pts). Previously published post hoc MAVORIC data has shown trends to higher multicompartmental efficacy with Moga in MF and SS pts with increasing baseline blood tumour burden (Scarisbrick J, et al. Efficacy and Safety of Mogamulizumab by Patient Blood Classification. Presented at the 16th EADO Congress, 12–14 October 2020, Virtual). This subset of pts may experience increased risk of disease progression and worse survival (Agar 2010, Am Soc J Clin Oncol).

This post hoc analysis of MAVORIC data examined the efficacy of Moga and Vori in MF pts stratified by baseline blood classification, and analysed time to global response (TTR) for Moga by disease subtype.

Methods

In MAVORIC, pts were randomized 1:1 to receive either Moga (intravenous, 1.0mg/kg weekly for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or Vori (oral, 400mg daily). Vori pts who experienced disease progression or intolerable toxicity could cross over to the Moga treatment arm.

In this analysis, efficacy outcomes (progression free survival [PFS], global overall response rate [ORR], and time-to-next-treatment [TTNT]) by investigator assessment (IA) for MF pts (Moga, n=105; Vori, n=99) were stratified by baseline blood involvement, where B0 indicates absence of significant blood involvement and B1 and B2 indicate low- and high- blood tumour burden, respectively. Analysis of TTR by IA by disease subtype was performed for Moga-responders (N=52).

Results

Moga-treated MF pts showed numerically superior results compared to Vori pts for PFS, ORR and TTNT and there was a trend with Moga to improved results for all analysed endpoints with escalating baseline B-class (Figure). Superiority was seen from statistically significant results for Moga vs Vori for MF B1 pts for PFS (8.43 vs 2.83 mo, P=0.003) and TTNT (11.9 vs 3.13 mo, P=0.002), and for MF B2 pts for ORR (46.2 vs 9.1 mo, P=0.033).

TTR analysis by IA in Moga pts showed a more variable range of values for MF compared to SS; median (range) TTR was 3.07 (0.93–27.83) mo vs 4.72 (0.93–16.17) mo for MF and SS, respectively.

Conclusion

Moga-treated MF pts show a trend to improvement in PFS, ORR and TTNT with increasing blood tumour burden. Statistically significant improvement is seen for MF pts with blood involvement (B1 and B2) treated by Moga vs Vori. While median TTR with Moga is shorter in MF pts, the greater range suggests that in some cases, clinical responses may occur later than those in SS pts.