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819 Concurrent treatment with GM-CSF immunoembolization of hepatic metastases and systemic immune checkpoint inhibitors to overcome immune evasion in patients with metastatic uveal melanoma
  1. Natalie J Miller1,
  2. Jacob Leary1,
  3. William McCamy2,
  4. Joshua Veatch2,
  5. Evan Hall1,
  6. Wayne Monsky1 and
  7. Shailender Bhatia1
  1. 1University of Washington, Seattle, WA, USA
  2. 2Fred Hutchinson Cancer Center, Seattle, WA, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Uveal melanoma (UM) is a poorly immunogenic melanoma subtype with low objective response rate (ORR) to immune checkpoint inhibitors (ICI). With a strong predilection for hepatic metastases, UM patients often receive liver-directed therapies, such as hepatic artery embolization. We hypothesized that transarterial immune-embolization (TAIE) with GM-CSF to treat hepatic metastases may synergize with concurrent use of ICIs, plausibly through improved antigen presentation.

Methods This single-center retrospective study includes UM patients with liver-predominant metastatic disease who received TAIE using a combination of GM-CSF (2000 mcg) and lipiodol for up to 10 treatments in an alternating lobar fashion, with/without concurrent systemic ICI (defined as administered within 3 months of starting TAIE). Efficacy endpoints included investigator-assessed ORR per RECIST 1.1, progression-free survival (PFS) and overall survival (OS). Safety endpoints included adverse events (AEs), related to TAIE and/or ICI.

Results Between 2016–2023, 18 metastatic UM patients (8M; 10F) with median age 64 (range 46–80) years received 83 IE treatments (median 3, range 1–10). Median follow up was 19.3 (range 1.7 – 47.1) months. Fourteen of 18 (78%) patients received concurrent ICI (n = 10 with combination anti-CTLA-4/PD-1, n = 4 with anti-PD-1). ORR was 17% (3/18), with all 3 patients experiencing partial responses lasting 4.2, 28.1+ and 38.6 months, respectively, while receiving concurrent ICI. Seven (39%) patients had stable disease as best response, resulting in a disease control rate of 56% (10/18). Median OS from first TAIE treatment was 35 (range 1.7- 39.2+) months. Concurrent IE with ICI was generally tolerated well, except one of 13 (8%) patients requiring hospitalization for transient distributive shock (n=1), which resolved with supportive care. Immune-related AE (IRAE) were only observed in patients receiving combination ICI with anti-CTLA-4/PD-1, including hepatitis (n= 5; G2 in 1 and G3 in 4; 4 required steroids and all resolved), pneumonitis (n=1; G1), pancreatitis (n=1, G2), colitis (n=1; G3) and adrenal insufficiency (n=1; G3); four of these seven patients resumed PD-1 monotherapy without further AEs.

Conclusions Concurrent administration of liver-directed therapy with GM-CSF TAIE and systemic ICI, including anti-CTLA4/PD-1 combination, is safe and feasible, and can lead to sustained clinical benefit in a subset of UM patients. For this poorly immunogenic cancer with a characteristic predilection for hepatic metastases, liver-directed novel immunotherapy approaches offer a unique opportunity to synergize with systemic immunotherapies.

Ethics Approval University of Washington IRB Committee D approved the study: Clinical Outcome of Immunotherapy in Melanoma and Other Skin Cancer

Patients, Investigator: Shailender Bhatia, IRB ID: STUDY00011495. IRB determined that consent was waived due to minimal risk.

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