Real-world Outcomes of Immunosuppressed Patients with Merkel Cell Carcinoma Treated with Immune Checkpoint Inhibitors.

9587 Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer that disproportionately affects older adults & the immunosuppressed. Immune checkpoint inhibitors (ICI) are highly effective in advanced MCC (aMCC), but pivotal ICI trials excluded immunosuppressed patients, highlighting an unmet need for this cohort. Methods: Clinical databases from 10 centers across 3 countries, were retrospectively analysed to identify immunosuppressed patients with aMCC who have received ICI. These patients were categorized into solid organ transplant (SOT), human immunodeficiency virus (HIV), hematological malignancies (HM) & autoimmune (AI) diseases. The overall aim was to assess treatment outcomes in patients excluded from trials. Results: This retrospective multicenter study identified 46 immunosuppressed patients (80% male) with aMCC and treated with ICI. The median age was 72 years (Table 1). The objective response rate (ORR) to anti-PD1/PDL1 ICI was 47.8%, with median progression-free survival (PFS) & overall survival (OS) of 23.4 & 40.9 months, respectively. 56.5% of patients have died at data cutoff. Cause of death included MCC (69.2%), comorbidities/others (15.4%), hematological malignancies (11.5%), and ICI-pneumonitis (3.9%). There were no deaths from graft failure, AI diseases or HIV. 8.7% developed ≥ grade 3 ICI-related adverse event (irAE). There was no difference in ORR (44% vs. 40%), OS (43.6 vs. 40.5 months, p = 0.68) or PFS (26.7 vs. 22.6 months, p = 0.18) in patients who experienced any grade irAE compared to those who did not. Clinicians were less likely to offer first line ICI to SOT patients (60%), particularly non-renal SOT patients 50%, compared with non-SOT immunosuppressed patients (89%). SOT patients had numerically lower response rates vs. non-SOT patients (ORR 30% vs 56%), significantly shorter PFS & OS at 6.5 months vs. 34.6 months (p= 0.001) & 13.1 months vs. 47.6 months (p = 0.002), respectively. Conclusions: Real world data shows that immunosuppressed MCC patients derive significant clinical benefit from ICI with acceptable rates of irAEs. Majority of immunosuppressed MCC patients (69%) died of disease progression, with 3.9% dying from an irAE & 11.5% from deterioration in HM. This suggests pre-existing immunosuppression should not significantly deter the use of ICI in patients with MCC. Patients with SOT have worse outcomes when treated with ICI compared with other immunosuppressed groups. Clinicians were more likely to reserve ICI use beyond first line. Study cohort. SOT (n=10) HIV (n=4) Autoimmune disease (n=16)* Hematological malignancy (n=16) Median Age (Range) 72 (18-90) Male, n (%) 37 (80) ORR (%) 30 100 56 38 Use of ICI First Line (%) 60 100 81 94 PFS months (95% CI) 6.5 (0.6 – 12.5) 41.1 (15.4 – 66.8) 34.9 (13.3 – 56.5) 20.8 (8.1 – 33.5) OS months (95% CI) 13.1 (2.3 – 24.0) Not reached 44.2 (22.8 – 65.5) 39.1 (23.4 – 54.8) *15 on treatment.