D1.187 - A Novel Volume-Reduced Desensitization Protocol for Pembrolizumab Hypersensitivity in Advanced Lung Cancer

Introduction

Introduction Pembrolizumab, an anti-PD-1 monoclonal antibody, is a critical therapy for non-small cell lung cancer (NSCLC) but carries a risk of infusion-related reactions (IRRs) and anaphylaxis. For patients with severe hypersensitivity and concurrent compromised pulmonary function, standard desensitization protocols may pose risks due to fluid overload or rapid dose escalation. We present a novel, fluid-restricted 16-step desensitization protocol designed to safely reintroduce pembrolizumab in a high-risk patient.

Case Report

A 50-year-old male with advanced stage IVb pleomorphic carcinoma of the lung (cT4N3M1c) and high PD-L1 expression (98%) experienced severe anaphylaxis during his second cycle of pembrolizumab. The reaction was characterized by tachycardia, dyspnea, flushing, and profound shock.

Given the patient's compromised pulmonary status and the risk of fluid overload, a custom 16-step desensitization protocol was developed (Table 1). The total dose of 200 mg was prepared in reduced volumes using four solutions: A (0.005 mg/mL), B (0.05 mg/mL), C (0.5 mg/mL), and D (5 mg/mL), totaling minimal fluid volume. The protocol began with Solution A (0.00125 mg) over 15 minutes, with dose doubling at each subsequent step.

During Step 15 (Solution D, cumulative dose 97.36 mg), the patient developed urticaria and right eyelid angioedema. The infusion was immediately paused, and antihistamines were administered. Once stabilized, the protocol was resumed at Step 13. The infusion rate was then maintained without further escalation, allowing the remaining dose to be administered successfully without recurrent anaphylaxis.

Discussion

We utilized a 16-step protocol rather than the standard 12-step approach to allow for more gradual antigen re-introduction given the severity of the initial shock. Crucially, the protocol prioritized high-concentration solutions to minimize total fluid volume, mitigating respiratory risks. This case demonstrates that a modified, volume-reduced 16-step desensitization protocol is a safe and effective strategy for continuing life-prolonging immunotherapy in patients with severe hypersensitivity and pulmonary comorbidities.

Conclusion

We have developed a 16-step desensitization protocol with fluid restriction for managing pembrolizumab-induced anaphylaxis in lung cancer patients.

Consent

Written informed consent was obtained from the patient for the publication of this case report.