Characterization of Skin Response in Patients with Mycosis Fungoides and Sezary Syndrome Treated with Mogamulizumab: A Retrospective, Real World Cohort
Authors: Christensen Rachel , Stuver Robert , Dusza Stephen , Epstein-Peterson Zachary D. , Ghione Paola , Horwitz Steven , Johnson William T. , Moskowitz Alison , Myskowski Patricia , Pulitzer Melissa , Geller Shamir 
Published: December 2024

Introduction: Mogamulizumab is a monoclonal antibody that targets chemokine receptor CCR4 and is indicated for the treatment of relapsed/refractory mycosis fungoides (MF) or Sézary syndrome (SS). The MAVORIC trial demonstrated that in patients with MF or SS receiving mogamulizumab, 68% achieve blood response and 42% achieve skin response (Kim, 2018). While the effect of mogamulizumab on the blood component in MF/SS is well established, the demographic, clinical, and treatment factors that underlie a patient's likelihood of achieving a skin response remain poorly understood. This study's objective was to comprehensively characterize skin responses achieved on mogamulizumab therapy.

Methods: Our single-center, retrospective cohort included patients with MF and SS with cutaneous involvement who had received at least one cycle of mogamulizumab with follow-up at our institution. Variables related to demographics, disease staging, prior therapies, mogamulizumab therapy, and clinical response, based on the United States Cutaneous Lymphoma Consortium criteria (Olsen, 2011), were collected using clinical records and sequential digital photographs. Patients were categorized into a skin response group, defined as 50-100% clearance of skin disease from baseline, or a skin non-response group, defined as &lt;50% clearance in skin disease from baseline. The best blood response achieved during mogamulizumab treatment was identified using sequential peripheral blood flow cytometry results. Blood response was defined as achieving B0 staging or a ≥50% decrease in the absolute numbers of neoplastic cells/µl compared to baseline. Descriptive statistics and univariate analyses comparing skin responders and non-responders were performed.

Results: In total, 56 patients (MF=35; SS=21) were included. Skin response was observed in 24 (43%) patients overall, 12 (34%) patients with MF, and 12 (57%) patients with SS (p=.09). The median time to best skin response was 2.3 months overall, 2.2 months (range 0.5-4.2) in patients with MF, and 3.0 months (range 1.2-6.4) in patients with SS (p=.09). Of the 30 patients with blood involvement, 28 (93%) demonstrated a blood response (89% of MF patients and 95% of SS patients; p=.52). Median time to best blood response was 1.8 months overall with no differences between MF and SS patients. Overall skin response was associated with higher clinical stage (p=.04) and higher B stage (p=.03). All 12 SS patients achieving a skin response also demonstrated a blood response. Of the SS patients achieving blood response, 12 (60%) demonstrated skin response.

In the MF cohort, higher advanced disease stage trended with higher percentage of patients achieving skin response, although this did not reach statistical significance (p=.07): only 2/16 patients (13%) with early-stage disease (IA-IIA) had skin response (both patients with stage IB and B0 [0.06 neoplastic cells/µl and 0.12 neoplastic cells/µl, respectively]) while in advanced-stage patients (IIB-IVB), 10/19 (53%) were skin responders. Of the 12 MF patients with a skin response, 6 had patch/plaque disease (T2), 1 had tumors (T3), and 5 had erythroderma (T4) (p=.13). Decrease in the absolute numbers of neoplastic cells/µl with mogamulizumab treatment was associated with skin response in the MF cohort (p=0.02). In the MF cohort only, skin response was also associated with fewer prior systemic therapies (p=.004).

Conclusion: Mogamulizumab may be more effective in inducing a skin response in patients with late-stage MF/SS and higher B stage, and skin responses in early-stage MF are uncommon. In our cohort, most patients with blood response also demonstrated skin response, with blood typically responding earlier than skin. Our findings, however, require confirmation in a larger cohort. An improved understanding of the characteristics influencing skin response in MF/SS patients and mogamulizumab treatment have implications for guiding treatment decisions.