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. 2021 Apr 30:11:662954.
doi: 10.3389/fonc.2021.662954. eCollection 2021.

Radiation Recall Pneumonitis After Treatment With Checkpoint Blockade Immunotherapy: A Case Series and Review of Literature

Paul Riviere  1 , Whitney Sumner  1 , Mariel Cornell  1 , Ajay Sandhu  1 , James D Murphy  1 , Jona Hattangadi-Gluth  1 , Andrew Bruggeman  1 , Sangwoo S Kim  1 , J Michael Randall  2 , Andrew B Sharabi  1
Affiliations

Radiation Recall Pneumonitis After Treatment With Checkpoint Blockade Immunotherapy: A Case Series and Review of Literature

Paul Riviere et al. Front Oncol. .

Abstract

Background: Radiation recall pneumonitis (RRP) is a poorly understood clinical syndrome in which patients develop radiation pneumonitis triggered by a systemic agent, often years after the completion of radiation therapy. Immune checkpoint blockade agents have only recently been posited as a trigger for RRP. Here, we present three cases of immunotherapy-induced RRP.

Case presentation: Our first patient was diagnosed with primary lung adenocarcinoma, and 4.5 years after completing radiation therapy developed symptomatic RRP immediately following a second dose of nivolumab-containing immunotherapy regimen. Our second patient was diagnosed with primary bladder cancer metastatic to the mediastinum, which was treated twice with radiation therapy. He developed RRP in the days following his second course of ipilimumab-pembrolizumab which was months after his second course of radiation that he received. Our final patient was diagnosed with metastatic small cell lung cancer and received local consolidative radiation therapy in addition to whole-brain radiation. He developed RRP on the 11th day after concluding his 4th cycle of nivolumab-ipilimumab, approximately 7 months after having had completed chest radiation therapy.

Conclusions: Immunotherapy-induced RRP is a rare diagnosis which can present more focally than traditional immunotherapy pneumonitis and which must be clinically differentiated from other local processes such as pneumonia. Further research should explore the mechanisms underlying these radiation recall reactions as many patients receive radiation and immunotherapy during the course of their cancer treatment.

Keywords: PD-1; checkpoint; immunotherapy; pneumonitis; radiation; reaction.

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Conflict of interest statement

AS reports research funding and honoraria from Pfizer and Varian Medical Systems, and consultant fees from AstraZeneca and Merck. ABS is the scientific founder and has an equity interest in Toragen Inc. outside the submitted work. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Patient 1's initial treatment plan, post treatment CT, CT at time of presentation with radiation recall, and CT following course of steroids with interval improvement.
Figure 2
Figure 2
Patient 2's treatment plan, post treatment CT, CT at time of presentation with radiation recall, and CT following course of steroids with interval improvement.
Figure 3
Figure 3
Patient 3's treatment plan, post treatment CT, CT at time of presentation with radiation recall, and CT following course of steroids with interval improvement.
See this image and copyright information in PMC

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