Single Dose Nivolumab and Ipilimumab Treatment Causing Complete and Durable Response in Extensive Stage Small Cell Lung Cancer Complicated By Severe Sensory Autoimmune Neuropathy

Document Type

Conference Proceeding

Publication Title

Journal of the National Comprehensive Cander Network

Abstract

Introduction: Immune check point (ICI) therapy has become an important component of treatment for small cell lung cancer (SCLC). However, in contrast to non-small cell lung cancer (NSCLC), response rates are lower and almost always transient in nature.

Background: To describe a dramatic and durable response to combined ICI therapy in a woman with metastatic SCLC, unfortunately also associated with severe ICI neurotoxicity.

Presentation: 55-year-old-female with smoking history, was found to have a right lower lobe perihilar mass with mediastinal invasion, mediastinal and right supraclavicular lymphadenopathy, a small right pleural effusion, and liver and pancreatic metastasis on imaging. Lymph node and pleural fluid sampling revealed neoplastic cells strongly positive for synaptophysin, CD56, TTF, Ae1/Ae2 keratin in dot-like-pattern and negative for p40 (Ki67 proliferation index was >90%), confirming SCLC. Following four cycles of etoposide+carboplatin she had interval progression. She received one dose of nivolumab and ipilimumab. Severe distal upper and lower limb pain and numbness was reported on her first outpatient follow up two weeks later. She had transient improvement with steroids and IVIG but progressed a few weeks later to develop severe sensory ataxia, loss of smell and taste, with motor sparing.

Management and Outcome: MRI brain was normal and repeat surveillance imaging two months following ICI therapy showed complete radiographic response. A course of Rituximab was administered with transient improvement but progression of her symptoms after discontinuation. Nerve conduction study was diagnostic of primary sensory axonal neuropathy of both distal upper and lower extremities with motor sparing. Paraneoplastic antibody panel showed P/Q Type-Calcium Channel and Acetylcholine Receptor Ganglionic Neuronal antibody positivity. Rituximab-hycela was resumed and continued (1400mg/3monthly) for 4 years with partial improvement and stabilization of symptoms. Interval imaging during her course continues to show complete clinical remission >5 years since ICI therapy.

Conclusions: This case describes a dramatic and durable response of SCLC to combined ICI blockade without chemotherapy. Also we hypothesize the relationship between severe ICI toxicity and durable response, as well as the potential role of anti-neuronal antigen immune activation producing profound anti-tumor effect but also leading to severe autoimmune toxicity.

DOI

https://doi.org/10.6004/jnccn.2024.7147

Publication Date

Spring 2025

Comments

Abstract: CLO25-069

e-ISSN

1540-1413

Link to Full Text

Share

COinS