Background

MAVORIC, a phase 3, randomized trial, evaluated mogamulizumab (Moga) safety and efficacy vs vorinostat (Vori) in patients (pts) with relapsed/refractory mycosis fungoides (MF) or Sézary syndrome (SS) (NCT01728805). Moga-associated rash (MAR) was the second most common TEAE in the Moga treatment arm and most common TEAE leading to treatment discontinuation (7% discontinuation rate, 13/184). Grade 1-2 and 3 drug rashes (DR) occurred in 20% (36/184) and 4% (8/184) of Moga pts, respectively. This analysis describes histopathological and other DR characteristics in MAVORIC Moga pts.

Methods

372 pts were randomized 1:1 to receive intravenous Moga (1.0 mg/kg once weekly for Cycle 1 (28 days); days 1 and 15 of subsequent cycles) or oral Vori (400 mg daily). Confirmed overall response rate (complete response + partial response) was based on a global composite response involving all four disease compartments, verified at two consecutive visits. Pts with an initial Grade 1 DR could continue treatment, using topical steroids as needed. For Grade ≥2 DR pts, Moga was temporarily stopped and topical steroids treatment advised. Systemic steroids were prohibited. Treatment could resume if DR resolved to Grade ≤1 within 2 weeks.

Results

This analysis included 44 Moga pts with DR, with results showing heterogenous histological patterns. Pathologically, central review assessed DR as granulomatous, histiocytic spongiotic, lichenoid, eosinophilic, psoriasiform, or a combination with no predominant histological pattern. Of these pts, 59.1% (26/44) were ≥65 years of age, and more SS (56.8, 25/44) than MF pts (43.2%, 19/44) experienced DR. Median (Q1, Q3) exposure was 344 days (162, 652) in SS DR pts and 185 days (85, 463) in MF DR pts. Class of concurrent medication or immediate prior CTCL therapy did not impact incidence. The proportion of SS responders with DR was significantly higher than those without DR (P=0.02; Fig.); the proportion of MF responders with DR did not differ from those without DR (P=0.21). The median (Q1, Q3) time to onset of DR was 106 days (36, 254). Initial DR occurred after response to Moga in 70% (14/20) of pts who experienced both. In the DR cohort, 35 pts (80%) resumed Moga treatment upon initial DR resolution, after which, the median (Q1, Q3) duration of exposure to Moga was 183 days (58, 332).

Conclusion

MAR displayed heterogeneous histopathology with no predominant feature; close correlation of suspected DR with clinical features is advised to differentiate it from disease progression. A trend toward higher DR rate was seen in SS pts, the group more likely to respond to Moga. DR may be attributable to increased exposure, but may also involve underlying disease characteristics or treatment-induced immune alterations, warranting further study. That 80% of pts on trial were able to continue Moga for >6 months following DR resolution suggests that appropriate evaluation, identification, and management may prevent premature discontinuation.