Higher levels of blood tumor involvement were linked with more favorable outcomes in patients who received treatment with mogamulizumab compared with vorinostat in patients with 2 types of cutaneous T-cell lymphoma.
Higher levels of blood tumor involvement were linked with more favorable outcomes in patients who received treatment with mogamulizumab (Poteligeo) compared with vorinostat (Zolinza) in patients with 2 types of cutaneous T-cell lymphoma (CTCL): mycosis fungoides (MF) and Sézary syndrome (SS), according to results from a post hoc analysis of the phase 3 MAVORIC trial (NCT01728805).1
Results from the trial, which are being presented during the 16th European Association of Dermato Oncology Congress, demonstrated that the overall progression-free survival (PFS) per investigator assessment was significantly higher with mogamulizumab versus vorinostat, at 7.7 months versus 3.1 months, respectively (P <.0001). When stratified by blood classification, data showed that the PFS was significantly greater for those with higher levels of blood involvement with mogamulizumab versus vorinostat.
“In MF and SS, assessing the stage of disease is key to prognosis, appropriate treatment, and patient outcome,” said Julia Scarisbrick, MBChB, FRCP, MD, lead author of the study analysis and consultant dermatologist.1 “Assessment of blood involvement is part of this staging process. The data highlight that mogamulizumab is more effective in [patients with] MF and SS who have blood involvement as part of their disease.”
“Blood involvement is relatively common in the more advanced stages of CTCL and may be present in as many as 20% of less advanced cases,” added Scarisbrick.2 “This new information could help improve the clinical management of [patients with] MF and SS and highlights the need for blood monitoring.”
In the open-label, multicenter, randomized phase 3 trial, investigators set out to examine the safety and efficacy of mogamulizumab versus vorinostat in patients with MF or SS who had progressed on at least 1 prior course of systemic therapy.3 In the trial, a total of 372 patients were randomized 1:1 to receive either intravenous (IV) mogamulizumab at 1.0 mg/kg on days 1, 8, 15, and 22 of the first cycle and days 1 and 15 of subsequent cycles (n = 186) or oral vorinostat at 400 mg once daily (n = 186).
Additional results from the updated analysis showed that mogamulizumab significantly improved responses compared with vorinostat; the overall response rates (ORRs) were 28% versus 5%, respectively (P <.0001). This held true in the analysis, as well; mogamulizumab elicited a significantly greater ORR in those with B2 blood classification compared with vorinostat. However, the agent did not lead to a significant improvement in ORR in those with B1 blood classification.
In patients without blood involvement, the difference in time-to-next treatment (TTNT) was not determined to be statistically significant between the 2 treatment arms. However, for those with B1 or B2 blood involvement, mogamulizumab significantly extended the TTNT compared with vorinostat, at 13.70 months versus 3.30 months, respectively (P <.0001).
With regard to safety, treatment-emergent toxicities proved to be comparable between the 2 treatment arms, irrespective of blood involvement; however, these effects were reported to be lower with mogamulizumab compared with vorinostat at each blood classification level.
Previously, results from a final safety analysis done in 370 patients who received study drug were reported.3 The median duration of follow-up was 34.5 months in the randomized portion of the trial, and median treatment exposure was 170 days for mogamulizumab and 84 days for vorinostat.
All-grade treatment-emergent adverse effects (TEAEs) were similar between the 2 arms; these toxicities included constipation, peripheral edema, headache, and anemia. TEAEs that were reported at a higher frequency in the investigational arm versus the control were infusion-related reactions (33.2% vs 0.5%, respectively) and drug eruption (25.0% vs 1.1%). However, the majority of the effects were grade 1 or 2 in severity.
The AEs attributed to mogamulizumab via investigator assessment included infusion-related reaction (33.2%), drug eruption (23.9%), and fatigue (18.5%). Toxicities attributed to vorinostat included diarrhea (55.4%), nausea (38.2%), and fatigue (33.3%).
In participants who crossed over from the control arm to the investigational arm and received the study treatment (n = 135), the most frequently experienced toxicities attributable to mogamulizumab included infusion-related reaction (37.8%), drug eruption (24.4%), fatigue (7.4%), alanine aminotransferase increase (7.4%), and aspartate aminotransferase increase (7.4%). Serious drug-related AEs proved to be comparable between the 2 treatment arms and in the patients who crossed over.
Additionally, 21.7% of those who received mogamulizumab discontinued treatment due to toxicities versus 23.7% of those who were given vorinostat and 25.9% of those who crossed over. The most common toxicities that resulted to discontinuation of study drug were drug eruption in the investigational arm (7.1%) and fatigue in the vorinostat arm (4.3%).
“We welcome the results of this analysis in furthering our understanding of the role of mogamulizumab in treating [patients with] MF and SS,” said Danie du Plessis, executive vice president of Medical Affairs at Kyowa Kirin.1 “Research suggests that patients with B1 and B2 blood classifications may have reductions in median survival and an increased risk of disease progression, compared with those classified as B0.4 Through our work with this therapy, we are aiming to address the unmet needs in these patient populations and are dedicated to improving outcomes for [patients] with MF and SS.”