Mogamulizumab Shines in Relapsed Cutaneous T-Cell Lymphoma

Cutaneous T-cell lymphoma (CTCL) is a less common subtype of non-Hodgkin lymphoma (NHL) for which there are relatively few effective treatment options. Mogamulizumab is a monoclonal antibody targeting chemokine receptor 4 (CCR4), a receptor that is frequently overexpressed on CTCL cells. In a phase I/II trial, mogamulizumab was found to be safe and effective in patients with CTCL, with an overall response rate (ORR) of 37%. At the 2017 American Society of Hematology  Annual Meeting & Exposition, Youn H Kim, MD (Stanford Cancer Institute, Stanford, California, United States), presented results from the large, randomized phase III MAVORIC trial (N = 372), which compared mogamulizumab (1.0 mg/kg weekly for 4 weeks and then every 2 weeks after) to vorinostat (400 mg daily) in patients with CTCL who had progressed on one or more systemic therapies. Patients on the vorinostat arm were allowed to cross-over to mogamulizumab following progression or unacceptable toxicity.

The median progression-free survival (PFS) was 7.7 months for patients treated with mogamulizumab, compared to 3.1 months for patients treated with vorinostat (hazard ratio [HR] 0.53, P<.0001). The PFS benefit of mogamulizumab was seen in all prespecified subgroups, including by disease type. Overall response rate was significantly improved in patients receiving mogamulizumab (28.0% vs 4.8%; P<.0001). For patients who were originally treated with vorinostat who elected to cross-over to the mogamulizumab arm, the ORR was 30.1%. Responses to mogamulizumab occurred more rapidly than responses to vorinostat (3.32 months vs 5.10 months) and were more durable (14.1 months vs 9.1 months). Importantly, responses to mogamulizumab were evaluated using global response criteria evaluating responses across multiple organ systems, rather than historic criteria that only evaluated responses in the skin.

Mogamulizumab was associated with a mostly mild toxicity profile. The adverse events occurring more commonly in patients treated with mogamulizumab were infusion-related reactions (33.2% vs 0.5%) and skin eruptions (23.9% vs 0.5%). Patients reported significantly greater symptom reduction and improved functional status with mogamulizumab.

In her conclusion, Dr Kim discussed the unmet need for new treatments for CTCL and highlighted that the MAVORIC trial is the first randomized phase III trial in CTCL to demonstrate a PFS benefit compared to vorinostat using global composite response criteria. Given the superior efficacy outcomes with mogamulizumab compared to vorinostat, Dr Kim indicated that mogamulizumab should become a new treatment option for patients with relapsed CTCL. Mogamulizumab is currently under priority review by the United States Food and Drug Administration for this indication.


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