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Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.046
vdae090.046
Final Category: Immuno-Oncology Approaches
AcademicSubjects/MED00300
AcademicSubjects/MED00310
IMUN-08 DURABLE RESPONSE TO IPILIMUMAB-NIVOLUMAB (IPI-NIVO) IN ANTI-PD1 REFRACTORY MERKEL CELL CARCINOMA WITH LEPTOMENINGEAL DISEASE PROGRESSION
Kennedy Lucy Boyce Cleveland Clinic Foundation, Cleveland, USA

Diaz Claudia Marcela Cleveland Clinic Lerner Research Institute, Cleveland, USA

Cordova Christine Cleveland Clinic Foundation, Cleveland, USA

Dhawan Andrew Cleveland Clinic Foundation, Cleveland, USA

Balagamwala Ehsan Cleveland Clinic Foundation, Cleveland, USA

Koyfman Shlomo Cleveland Clinic Foundation, Cleveland, USA

You Jee Young Cleveland Clinic Foundation, Cleveland, USA

Chao Samuel Cleveland Clinic Foundation, Cleveland, USA

Suh John Cleveland Clinic Foundation, Cleveland, USA

Angelov Lilyana Cleveland Clinic Foundation, Cleveland, USA

Isaacs James Cleveland Clinic Foundation, Cleveland, USA

Ko Jennifer Cleveland Clinic Foundation, Cleveland, USA

Chan Timothy Cleveland Clinic Lerner Research Institute, Cleveland, USA

Truong Thach-Giao Cleveland Clinic Foundation, Cleveland, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i15i15
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

Leptomeningeal disease (LMD) is a rare complication of Merkel cell carcinoma (MCC), which has been described in limited case reports, none of which describe outcomes with IPI-NIVO. Here we describe a patient with PD-1 refractory MCC LMD with durable response to IPI-NIVO. A 69-year-old male diagnosed with stage IIIA MCC underwent left groin dissection and radiation. He developed recurrence in distant lymph nodes and started pembrolizumab (PEMBRO). Seven months after starting PEMBRO, he developed lower extremity weakness. Spine MRI showed LMD involving cauda equina. CSF testing detected tumor cells. Imaging did not show any recurrence aside from LMD. He received radiation to L1-S2 followed by IPI-NIVO. His LMD has remained clinically and radiographically stable 10 months after starting IPI-NIVO. Longitudinal circulating tumor DNA (ctDNA) monitoring demonstrated clearance both after starting PEMBRO and IPI-NIVO. ctDNA was detectable 5 weeks after starting PEMBRO and 5 months after starting IPI-NIVO and became undetectable 10 weeks after starting PEMBRO and again 8 months after starting IPI-NIVO. We prospectively collected peripheral blood at baseline prior to PEMBRO, when LMD developed, with cycle 3 IPI-NIVO, when he developed pneumonitis 4 months from cycle 1, and following CNS and systemic tumor clearance at 7 months from cycle 1 of IPI-NIVO with patient on maintenance NIVO alone. Peripheral flow cytometry, quantitative proteomics, and serum cytokines were used to characterize immune cell numbers and phenotypes in this exceptional responder. Kinetics of immune correlates, including CD33+HLADRlo, CD15+CD14-MDSC, CD57+ CD8+ T cells, showed distinctive changes during the clinical course. This case demonstrates unique response to IPI-NIVO with durable neurologic stability and confirmatory ctDNA clearance in a patient with PD-1 refractory MCC and less common CNS progression with documented LMD. Although the prognosis of MCC LMD is poor, this patient achieved an objective CNS response, and we reversed PD-1 resistance with IPI-NIVO.
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