Long‐term outcomes with mogamulizumab alone or in combination with other therapies for the treatment of cutaneous t‐cell lymphoma

Introduction: Mogamulizumab (MOGA) is an anti-CCR4 monoclonal antibody approved for mycosis fungoides (MF) or Sézary syndrome (SS). The MAVORIC trial comparing MOGA versus vorinostat showed superior overall response rates (ORR) (28% vs. 4.8%, P < 0.0001) and progression free survival (PFS) (7.7 vs. 3.1 months (mo), P < 0.0001) with MOGA. We report the long-term outcomes of patients (pts) treated with MOGA at Stanford. Moreover, we describe the impact of MOGA-associated rash (MAR) and MOGA combination therapies (combotx) in the treatment outcomes. Methods: We obtained the data from MF and SS pts who were treated with MOGA from 2009 to 2022. We evaluated ORR (consensus criteria), duration of response (DOR), time to next treatment (TTNT), PFS, OS, impact of MAR and of combotx. Combotx was defined as the intended use of concurrent or sequential treatment(s) to augment clinical response and/or as a supportive therapy for MAR. TCR clonality data was used to confirm MAR. TTNT was defined as time from initiation of MOGA mono or combination therapy to the initiation of the next systemic therapy for lymphoma. Results: A total of 65 pts were included: MF = 16, SS = 49. Median age was 68 (26–90). At the time of treatment, 20% had measurable nodal (N3) disease, 14% had a biopsy showing large cell transformation (LCT) within 5 years prior to MOGA, and 92% had disease stage IIB-IV. Median prior lines of systemic therapies was 3 (0–18). Median follow-up was 42 mo (1.3–148). Overall, median TTNT was 15 mo (95% CI: 10–23), PFS 25 mo (95% CI: 14–30), OS 127 mo (95% CI: 45–135). ORR was higher for SS (74% vs. 25%, p < 0.01); PFS and TTNT were longer in SS but not significant. LCT and N3 disease were associated with worse TTNT. Combotx was used in 32% pts, SS = 86%. ORR was higher in pts that received combotx compared to monotherapy (monotx) (95% vs. 45%, p < 0.0001). Combotx led to significant improvement in the rate of objective response lasting ≥12 mo (ORR12) (90% vs. 55%, p = 0.03), TTNT (38 vs. 10 mo, p = 0.0018) and PFS (39 vs. 14 mo, p = 0.0274). Proportion of LCT and N3 between groups was not significantly different. Agents used in combotx included methotrexate, oral retinoids, total skin electron beam therapy, and magrolimab. MAR occurred in 49% pts (MAR+), SS = 88%. ORR was 91% in MAR+ versus 33 % without MAR (MAR-). MAR+ had significant improvement in the ORR12 (86% vs. 36%, p = 0.0037), TTNT (30 vs. 7.5 mo, p < 0.0001) and PFS (30 vs. 11.5 mo, p = 0.0049). Proportion of LCT and N3 between groups was not significantly different. Duration of MOGA exposure was similar between MAR+ and MAR- and responders versus non-responders [figure]. Keywords: Cutaneous non-Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract. Y. H. Kim Consultant or advisory role: Corvus, CRISPR Therapeutics, Innate Honoraria: Kyowa Kirin, Citius, CRISPR, Takeda Research funding: Eisai/Citius, Kyowa Kirin, Innate, Trillium, Elorac, CRISPR Therapeutics, corvus