Radiation Recall Pneumonitis Induced by Anti-PD-1 Blockade: A Case Report and Review of the Literature

Abstract

Background: Radiation recall pneumonitis (RRP) is an unpredictable but relatively severe subclinical radiation damage which occurs in the previously irradiated fields of pulmonary tissue after administration of a systemic agent. Previous reports of RRP were mainly attributed to chemotherapy and molecular-target agents. RRP induced by immunotherapy has been rarely reported. Here we describe a case of a novel pattern of RRP induced by anti-PD-1 blockade Camrelizumab 2 years after radiotherapy, with some focus on further understanding of this phenomenon. Case Report: A 64-year-old man with non-small cell lung cancer (NSCLC) received two cycles of chemotherapy with cisplatin and pemetrexed first. Subsequently, he underwent concomitant chemoradiotherapy with cisplatin and pemetrexed to simultaneous integrated boost (SIB) radiotherapy. After 15 months, due to tumor progression and brain metastasis, he started with administration of anti-PD-1 blockade Camrelizumab (200 mg q2w) and stereotactic radiosurgery (SRS). The patient developed fever, dyspnea and cough after the eighth administration of Camrelizumab. Meanwhile, his chest CT revealed patchy consolidation and ground-glass opacities localized within the previously irradiated area. Subsequent treatment regimen was adjusted to 80 mg q12h prednisolone with discontinuation of Camrelizumab. Then the symptoms gradually eased and reexamination of CT showed significant improvement in RRP after 2 weeks. Conclusion: Our case report presents a novel pattern of RRP induced by anti-PD-1 blockade Camrelizumab 2 years after radiotherapy. This indicates that previous radiotherapy combined with subsequent anti-PD-1 blockade has a potential to cause overlapping damage to lung, suggesting that intensive attention might be needed for patients who are treated with anti-PD-1 blockade in conjunction with a prior history of thoracic radiation.

Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review

“…While the “long tail effect” and immunological memory of ICIs could also give rise to long-lasting AEs, which may contribute to the increased incidence of AEs when combined with subsequent RT. Moreover, immunotherapy followed by RT was also found to induce radiation recall pneumonitis, which was triggered by a “remembered” and “overreacted” process of the immunomodulatory effect ( 67 ). Thus, sequential treatment could not completely avoid the overlapping toxicity and significantly decrease the occurrence of AEs, as initially envisioned.…”

Rapid Development of Clinically Symptomatic Radiation Recall Pneumonitis Immediately Following COVID-19 Vaccination

“…Clinical symptoms may include a dry cough, low-grade fever, and shortness of breath [ 3 ]. Typical triggers include pharmacological agents, particularly chemotherapies, but nowadays it is increasingly described after the administration of targeted agents and ICI as well [ 1 , 2 , 4 , 9 ].…”

A Case of Suspected Radiation Recall Pneumonitis After a COVID-19 Infection

“…It was previously speculated that these factors induce resistance to additional chemotherapy and cause inflammatory responses. Notably, it is not only caused by non-cytotoxic drugs such as tamoxifen but also by recently developed immune checkpoint inhibitors [3][4][5]. Therefore, immunity is also considered to be an influencing factor, but the mechanism is still unknown.…”