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 S ezary syndrome (SS) who had failed ≥1 prior systemic therapy. Mogamulizumab significantly prolonged progression-free survival (PFS), with a superior objective response rate (ORR) vs. 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 vs. 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 + CD26cell 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 vs. vorinostat in patients with MF and SS classified as having B1 and B2 blood involvement.

Mogamulizumab-associated rash (MAR) mars its efficacy in the treatment of cutaneous lymphoma

“…In line with this, a subgroup analysis of the original MAVORIC cohort also identified a higher ORR in patients with SS with MAR 7 . Of interest, higher CTCL blood disease burden is associated with both higher likelihood of clinical response to mogamulizumab and higher probability of MAR 7,8 . Thus, the association of MAR with a superior clinical outcome in CTCL is promising and may be helpful as a predictor of response.…”

“…7 Of interest, higher CTCL blood disease burden is associated with both higher likelihood of clinical response to mogamulizumab and higher probability of MAR. 7,8 Thus, the association of MAR with a superior clinical outcome in CTCL is promising and may be helpful as a predictor of response. Nevertheless, it raises two important clinical points: (i) accurate diagnostic differentiation of MAR from CTCL disease progression, which may clinically look very similar and (ii) a treatment strategy in the context of active MAR.…”

Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study

“…Nevertheless, this first multicentric real-life data study supports the fact that mogamulizumab is efficient in 13/21 patients presenting late stage CTCL. Previous studies demonstrated that it is a safe drug [ 21 , 22 , 23 ], which makes it interesting in CTCL that are not responding to classical treatments.…”

The Treatment of Advanced-Stage Mycosis Fungoides and Sezary Syndrome: A Hematologist's Point of View.

“…This trial, however, was not powered to detect OS differences between the two groups within the defined follow-up period. 32 The most common adverse events associated with mogamulizumab were mostly graded 1–2 and manageable (infusion-related reactions [37%], skin eruptions [25%], and diarrhea [14%]). Pyrexia (4%) and cellulitis (3%) were the most common grade 3 adverse events in the mogamulizumab group.…”