Outcomes in octo- and nonagenarians treated with mogamulizumab-based regimens for cutaneous T-cell lymphoma

Abstract Introduction: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL), with a median age at diagnosis of 55 years old. However, many patients (pts) are older, and its incidence is four-fold increased among pts over 70. As life expectancy rises, octogenarians will comprise an increasing proportion of the CTCL population; however, there are currently no consensus guidelines for managing this older demographic. Mogamulizumab (moga), a monoclonal antibody targeting C-C chemokine receptor 4 (CCR4),demonstrated remarkable efficacy in CTCL in the phase 3 MAVORIC trial. We sought to evaluate the effiacy and tolerability of moga-based regiments in patients aged 80 and older that were under-represented within this trial cohort. Methods: This single-center retrospective observational study included CTCL pts aged ≥80 who initiated moga therapy between December 2017 and December 2024, with at least 6 months of follow-up.Global treatment response was assessed by 2022 consensus criteria, and toxicity per CTCAE v5.0. Baseline characteristics were analyzed using independent t-tests, Fisher's exact tests, or Pearson's chi-square tests. Overall survival (OS) and progression-free survival (PFS) were co-primary endpoints analyzed via Kaplan-Meier log-rank and Cox proportional hazards models. Results: Nineteen pts were identified (13 SS [68%], 6 MF [32%]); median age was 82 (range:80–94). Ten (53%) were male and 16 (84%) were White. Thirteen (68%) had ECOG 0-1 and 15 (79%) had advanced stage disease. LDH was elevated in 15 pts (79%) and 8 (42%) had a history of large cell transformation. Median lines of treatment prior to moga was 3 (range:1-8). All pts received moga at 1 mg/kg on days 1, 8, 15, and 22 of cycle 1, then biweekly; 8 pts (42%) later transitioned to 3–4-week intervals. Combination therapy was used based on institutional practice in 13 pts (68%) including interferon alpha (6/13,46%), bexarotene (6/13,46%), interferon gamma (7/13,54%) and extracorporeal photopheresis (8/13, 62%). Two pts (11%) received total skin electron beam therapy during their treatment course. Median duration of moga treatment was 9 months (range 2-51 months). Seventeen pts (89%) achieved a global response (6/17 [35%] complete, 11/17 [65%] partial), while two (11%) had stable disease. Compartmental responses were highest in blood (15/16, 94%), followed by skin (17/19,89%) and nodes (2/3,67%). No pts exhibited visceral disease. Median length of follow up was 14.4 months (range: 6-72 months). Median duration of response was 10 months (range 3-49 months). Median PFS was 12.6 months (95% CI 6.8-32.3 months). Thirteen pts (68%) were alive at last follow-up; and median OS was not reached. Cause of death was attributable to CTCL in only one patient (5%) and there were no treatment-related deaths. Six pts (32%) experienced grade 1-2 infusion reactions, all manageable with subsequent additional premedication. Cytopenias were observed in 15 pts (79%) with 7/15 ( 46%) having grade 3 or 4 cytopenias. Biopsy confirmed moga-associated rash (MAR) was observed in 9 pts (47%) all of which resolved with topical corticosteroids (7/9, 78%) and/or oral methotrexate (2/9, 22%). Other notable non-hematologic adverse events included grade 2 thyroiditis in one patient (5%) and Grade 1-2 diarrhea in two pts (10.5%). Reasons for cessation of moga therapy included MAR (4,21%), progression of disease (5/19,26%) or patient preference (4/19, 21%). Six pts (32%) remained on therapy at last follow-up. Discussion: To our knowledge, this is the first real-world study to evaluate moga-based regimens in patients 80 or older with MF/SS. Notably, this patient population was largely not represented within the MAVORIC trial which led to moga approval for MF/SS. Our results suggest that moga-based treatment regimens have a significant therapeutic role in elderly pts with MF/SS, with an observed response rate of 89%, in line with our previously reported institutional experience. Given its safety and efficacy profile, moga -based regimens can play an important role in CTCL in elderly pts. However further investigation in prospective clinical trials is warranted to more clearly delineate efficacy in this patient population.