The size of the left lower lobe mass (arrow) decreased, suggesting a pseudoprogression on the previous study. Table 3: ICI Therapy–related Pneumonitis Patterns. NSIP-associated connective tissue and autoimmune disorders are generally long-standing processes in the setting of other known comorbid conditions. Abstract. (b) Axial chest CT image obtained 2 months later after starting pembrolizumab therapy shows bilateral lower lobe ground-glass and reticular opacities (black arrows), with regions of immediate subpleural sparing (white arrows). Reduced baseline pulmonary function and history of smoking may increase the risk of pneumonitis. (c) Follow-up axial chest CT image shows near-complete resolution of pneumonitis, with several remaining faint subpleural right lower lobe opacities (arrows). Pneumonitis is more likely to manifest in patients receiving ICI combination therapy compared with those receiving monotherapy (21). (b) Axial chest CT image obtained 4 months later after nivolumab therapy shows multifocal peripheral and subpleural mid- and lower-lung airspace consolidations (arrows), a finding consistent with an OP pattern of pneumonitis. (a) Baseline axial chest CT image shows a medial left lower lobe lung mass with surrounding ground-glass halo sign (arrow), a finding corresponding to adenocarcinoma. Illustration shows the global effect of irAEs with associated manifestations. Thus, blockade of key portions of either or both of these immune checkpoint pathways is thought to be responsible for the antitumoral activity with ICIs (Fig 1). ICI therapy–related pneumonitis is an irAE, potentially resulting in significant morbidity with possible discontinuation of therapy and possible mortality. Braschi-Amirfarzan M, Tirumani SH, Hodi FS, Nishino M. Immune-Checkpoint Inhibitors in the Era of Precision Medicine: What Radiologists Should Know. AIP–ARDS pattern of pneumonitis in a 57-year-old man undergoing nivolumab therapy for stage IV lung adenocarcinoma. While many ICI therapies are initiated after failure of first-line or established therapies, several drugs are approved as first-line therapies. However, changes of fibrotic NSIP in nontreatment-related cases including lower lobe volume loss and traction bronchiectasis have not been reported in ICI therapy–related pneumonitis, likely because cases are detected and treated in the acute stage. Immune-Related Adverse Event Guideline: Pneumonitis Severe new onset of symptoms limiting ARDS Invest calcium, CRP) antigen Pulmonary irAEs have been observed following treatment with immunotherapy and have occurred after a single dose and after as many as 48 treatments. (b) Axial chest CT image obtained 2 months after initiating trastuzumab therapy shows a focal region of ground-glass opacities within the posterior and medial left lower lobe (arrow), with a well-defined linear demarcation from the adjacent normal lung. Infection, including atypical and fungal causes such as invasive aspergillosis, should also be considered and often can be distinguished by clinical and laboratory findings. 58, No. Figure 3a. Subsequently, updated treatment response criteria such as the immune-related response criteria (irRC), immune-related RECIST (irRECIST), and immunotherapy RECIST (iRECIST) have been developed to account for these unique imaging features (10–12). Patient and drug-related factors predicting the development of pneumonitis are currently under investigation. (c) Follow-up axial chest CT image obtained 3 months later after withholding ICI therapy and administering steroid therapy shows resolved pneumonitis. Extensive bone metastatic disease. history of melanoma on the left side of the face (resected in December 2012) and metastasis to the left lung upper lobe (resected in November 2016). HP pattern may also mimic other small airways processes such as respiratory and follicular bronchiolitis, which are classically associated with smoking and underlying connective tissue or autoimmune disease history, respectively. Recurrent pneumonitis in a 78-year-old patient with small cell lung carcinoma. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Similar to the NSIP pattern, HP pattern is associated with lower-grade symptoms (median CTCAE grade 1) (31). Key differences in these updated criteria include the need for repeat imaging (ie, performed 4 weeks after initial response assessment) to confirm disease progression and the principle that the appearance of new lesions does not necessarily constitute disease progression. However, in some cases, nodules may be nodular and masslike with spiculated margins, simulating findings of malignancy (34). The patient was receiving anti-PD1 (nivolumab) to treat her advanced metastatic melanoma. Six weeks after starting nivolumab therapy, the patient presented with severely worsening dyspnea. While the increased activation of the immune system is responsible for the therapeutic efficacy of ICI therapy, it is also the driver behind the immune-related adverse events (irAEs) of these therapies. This latter category includes immune checkpoint inhibitor (ICI) therapy. ICI therapy–related pneumonitis manifests as several distinct radiologic patterns that overlap with other infectious and inflammatory conditions. Figure 1a. Immunotherapy was subsequently held, and steroid therapy was administered. NSIP pattern should be distinguished from atypical infectious processes, which can often be determined on the basis of clinical parameters. Spectrum of treatment-related pneumonitis among various therapy types. During PET/CT surveillance, ... delaying nivolumab for grade 2 & discontinuation of immunotherapy for grade 3 & 4 pneumonitis 2. Normally, an important function of T cells is in the cell-mediated clearance of tumor cells. Adjacent bronchial wall thickening is also frequently depicted (Fig 7). As opposed to conventional cytotoxic chemotherapy, which acts by a variety of mechanisms and stages of the cell cycle to directly interfere with cancer cell growth, cancer immunotherapy harnesses the immune system to limit the ability of cancer cells to evade the immune system and combat proliferation. Figure 2. Treatment is often effective, although recurrence is possible. Spectrum of treatment-related pneumonitis among various therapy types. Radiation recall pneumonitis in a 65-year-old woman with metastatic breast cancer. We describe the findings of a SARS-CoV-2 infection on PET/CT with 18 F- FDG in a 51-year-old man with metastatic renal cell carcinoma under treatment with nivolumab . 2017 and had a recorded diagnosis of pneumonitis related to immunotherapy. Figure 5b. Figure 9b. (a) Baseline axial chest CT image obtained before starting immunotherapy shows multiple lung nodules and masses. A smaller series by Nishino et al (31) with 20 pneumonitis cases described similar patterns as well as acute interstitial pneumonia (AIP)–acute respiratory distress syndrome (ARDS) occurring in 10% of patients. However, conventional imaging response criteria such as RECIST 1.1 have shortcomings in the evaluation of treatment response for ICI therapy, leading to the potential for premature cessation of therapy in patients who might otherwise show benefit with therapy (9). Depending on the severity and initial response, other agents such as infliximab, mycophenolate, or intravenous immunoglobulin may also be added. Figure 3b. (c) Follow-up axial chest CT image obtained 2 months later after steroid therapy shows resolved right lower lobe pneumonitis. 33 Everolimus and temsirolimus are specific inhibitors of mTOR and are used as anticancer therapeutic agents. Spectrum of treatment-related pneumonitis among various therapy types. Patients with grades 3 and 4 pneumonitis require permanent discontinuation of ICI therapy and more intensive care, requiring inpatient admission with close monitoring. If the address matches an existing account you will receive an email with instructions to reset your password. This axial CT image in lung windowing shows multifocal alveolar consolidations in a subpleural and peribronchovascular location, predominating at the level of the left upper lobe. Airspace disease is temporally homogeneous and relatively symmetric, with consolidative opacities uncommon, features that help in distinguishing NSIP from OP patterns. ■ Illustrate the imaging patterns of ICI therapy–related pneumonitis and related clinical classification schemes. For example, pembrolizumab, a PD-1 inhibitor, has FDA approval as frontline treatment of advanced epidermal growth factor receptor and anaplastic lymphoma kinase wild-type non–small cell lung cancer in which tumors have at least 50% PD-L1 expression. The symptoms improved on discontinuation of atezolizumab and a course of prednisone. The largest study to date by Delaunay et al (25) includes 64 cases of pneumonitis with the following CT patterns described: (a) OP (23%), (b) hypersensitivity pneumonitis (HP) (16%), (c) nonspecific interstitial pneumonia (NSIP) (8%), and (d) bronchiolitis (6%). Furthermore, the use of serum markers for the prediction and monitoring of ICI therapy–related pneumonitis is also an active area of investigation. Significant morbidity and mortality can result, and severe pneumonitis attributed to ICB precludes continued therapy. Recipient of a Certificate of Merit award for an education exhibit at the 2018 RSNA Annual Meeting. (c) Follow-up axial chest CT image shows near-complete resolution of pneumonitis, with several remaining faint subpleural right lower lobe opacities (arrows). Patients with grade 1 or 2 pneumonitis have no or milder symptoms and are typically managed as outpatients, while patients with grade 3 or higher require more intensive management. (b) Follow-up coronal chest CT image obtained 1 month later after withholding ICI therapy and administering steroid therapy shows resolved pneumonitis, with a return to near-baseline findings. Immune check… Higher rates of pneumonitis have been observed in non–small cell lung cancer and renal cell carcinoma versus those of melanoma (22). Grade 2 pneumonitis can be managed in the outpatient setting by withholding the ICI therapy and initiating steroid therapy, with initial dose burst followed by a 4- to 6-week taper. However, a combination of immunotherapy (pembrolizumab) with chemotherapy was not linked to an increased risk of pneumonitis in lung cancer . The size of the left lower lobe mass (arrow) decreased, suggesting a pseudoprogression on the previous study. Radiation recall pneumonitis in a 65-year-old woman with metastatic breast cancer. We describe the findings of a SARS-CoV-2 infection on PET/CT with F-FDG in a 51-year-old man with metastatic renal cell carcinoma under treatment with nivolumab. (b) Axial CT image in a 63-year-old woman undergoing gemcitabine therapy for pancreatic cancer shows bilateral subpleural reticular opacities, with background faint ground-glass and interstitial opacities (arrows) that are more pronounced in the left lower lobe. Pulmonary nodules may also be depicted, typically in a peribronchovascular distribution and more commonly as smaller nodules (<10 mm). Other immune cells and mediators such as B cells, granulocytes, and cytokines have also been implicated (16). (2018) memo - Magazine of European Medical Oncology. (c) Axial chest CT image obtained 1 month later after withholding ICI therapy and administering steroid therapy shows residual, although significantly improved, airspace disease (arrows). Immunotherapy was subsequently held, and steroid therapy was administered. Minimal subpleural ground-glass opacities in the right lower lobe were thought to be dependent atelectasis. 18 (1): 42-53. Radiation recall pneumonitis in a 65-year-old woman with metastatic breast cancer. Despite the presence of various cell-mediated immune response pathways, tumor cells have developed means of evading the natural tumor response system of the body. These ICI agents have adverse effects including the uncommon but potentially serious pulmonary toxicity of pneumonitis. ICIs act through a unique mechanism of action when compared with those of conventional chemotherapeutic agents. However, little is known about the clinical and radiological features of checkpoint inhibitor-induced lung disease. (c) Axial chest CT image obtained 5 months after discontinuation of therapy shows minimal residual (although markedly improved) pneumonitis (arrow) in the left lower lobe. OP pattern most commonly manifests as patchy bilateral opacities with a peripheral or peribronchovascular predominance, often with a mid- to lower-lung predominance (Fig 3). Combinations of PD-1 and CTLA-4 inhibitors with nivolumab and ipilimumab have also demonstrated higher irAE rates compared with those of respective monotherapies in patients with advanced melanoma (20). It has been advised that the immune checkpoint inhibitor regimen not be restarted until CT scans show improvement or there is complete resolution of pneumonitis. (c) Axial chest CT image obtained 5 days later after further respiratory decompensation (despite withholding ICI therapy and initiating intravenous steroid therapy) shows increasing severity and confluence of ground-glass opacities (arrows), with little intervening normal lung parenchyma. NSIP pattern is the second most commonly described pattern of ICI therapy–related pneumonitis, although it is diagnosed in a minority of reported cases. A subset of irAEs is pneumonitis, which is an important and potentially fatal complication of ICI therapy and is the focus of this article. Also, ICI therapy–related pneumonitis is more commonly associated with multiorgan involvement with other irAEs. ICI therapies are increasingly being used as first- and second-line agents in the treatment of a growing number of malignancies. To standardize terminology regarding treatment-related adverse events, pneumonitis symptoms are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) (26). 28, No. A majority of patients do not develop recurrence after restarting immunotherapy, although reports of rechallenge mainly describe patients with initial grade 1 or 2 pneumonitis. Despite treatment of pneumonitis, approximately one-fourth of patients will develop recurrence (21) (Fig 10). (b) Axial chest CT image obtained 2 months later after starting pembrolizumab therapy shows bilateral lower lobe ground-glass and reticular opacities (black arrows), with regions of immediate subpleural sparing (white arrows). Aspiration is typically found in the dependent lungs, with accompanying fluid or debris-filled airways, and esophagus, while infection can often be delineated clinically. (b) Axial chest CT image shows new multifocal ground-glass opacities (black arrows), with interval enlargement of several pulmonary masses (white arrows). (b) Axial chest CT image shows new multifocal ground-glass opacities (black arrows), with interval enlargement of several pulmonary masses (white arrows). HP pattern can often be differentiated from atypical infection on clinical grounds. Recurrent pneumonitis pattern, location of involvement, and severity may vary compared with those at initial presentation. Figure 4c. 5, World Chinese Journal of Digestology, Vol. (d) Axial CT image obtained after completing steroid therapy and restarting nivolumab therapy shows recurrence of an OP pneumonitis pattern with new areas of involvement (arrows). Sarcoidlike reactions demonstrate identical histopathologic features to those of sarcoidosis, namely noncaseating granuloma formation. After completing this journal-based SA-CME activity, participants will be able to: ■ Describe the indications and mechanisms of action of ICIs and the pathophysiology of ICI therapy–related pneumonitis. Described findings of HP pattern mirror those typically found in cases of subacute HP depicted in other settings. The diagnosis of immunotherapy-induced pneumonitis was made after careful exclusion of other pulmonary conditions such as infection and malignancy. The differential diagnosis for AIP–ARDS pattern is broad and includes pulmonary edema (often associated with other findings of cardiac failure), hemorrhage (associated with hemoptysis and underlying coagulopathy), and infection. The development of an irAE is mainly T-cell mediated, and infiltration of CD4 and CD8 cells has been observed in association with irAEs (15). The appearance and treatment of OP pattern ICI therapy–related pneumonitis are virtually indistinguishable from those of cryptogenic OP, although the latter is usually a long-standing process without a temporal relationship to the immunotherapy course. (a) Baseline axial chest CT image shows the lungs before immunotherapy was initiated. For example, patients receiving ICI therapy have shown greater susceptibility to the development of treatment-related pneumonitis, with increased risk of high-grade pneumonitis (45). Overall, the incidence of ICI therapy–related pneumonitis is estimated to be between 3% and 6% (21). Emergency presentations in patients treated with ICIs are a clinical challenge. Pneumonitis may manifest with other irAEs, such as dermatitis, colitis, and endocrinopathies (21). Sarcoidlike reaction has been most commonly reported in patients undergoing ipilimumab therapy and in those with melanoma (42). After pneumonitis resolution, clinicians are faced with the decision of whether to restart ICI therapy (ie, rechallenge). The mechanism of radiation recall reactions remains unclear, although possibilities include changes in the function of stem cells in the irradiated field versus idiosyncratic drug hypersensitivity reactions (39). (a) Baseline axial chest CT image shows the lungs before immunotherapy was initiated. (a) Baseline axial chest CT image shows the lungs after completion of radiation therapy. Immunotherapy has been withheld and, some weeks later, the lungs have improved and there are some residual perihilar upper lobes infiltrates. (b) Axial CT image obtained 2 weeks after starting nivolumab therapy shows a region of centrilobular solid and ground-glass nodularity (black arrows) in the right lower lobe. Although not specifically addressed in published guidelines given the potential for high steroid doses administered for extended periods, infectious prophylaxis may be warranted. Pneumonitis Related to Melanoma Immunotherapy. Immune-related adverse events are an increasingly recognized set of complications of ICI therapy that may affect any organ system. Many of these adverse events are unique from those previously observed with conventional chemotherapy regimens. In the presence of a foreign cell such as a tumor cell, antigen-presenting cells, including dendritic cells or macrophages, incorporate and present a tumor antigen through a major histocompatibility complex, which subsequently binds to a T-cell receptor. In cases of ICI therapy–related pneumonitis, the most common finding at bronchoalveolar lavage is T-lymphocytic alveolitis (25). Furthermore, basilar predominance and subpleural sparing in the NSIP pattern are less typical findings of infection. Minimal subpleural ground-glass opacities in the right lower lobe were thought to be dependent atelectasis. Also, tumors may increasingly express PD-L1 receptors causing decreased T-cell activity and tumor proliferation (7). COVID-19 Pneumonia Mimicking Immunotherapy-Induced Pneumonitis on 18F-FDG PET/CT in a Patient Under Treatment With Nivolumab. Recurrence of metastasis to the bilateral lungs and left pleura was detected in April 2018. Interlobular septal thickening and a “crazy-paving” pattern may also be present (34). Figure 7: Axial chest CT scans show programmed cell death protein 1 (PD-1) inhibitor–related pneumonitis in a patient with advanced non–small cell lung cancer treated with nivolumab. June 15, 2020 Within a few months, coronavirus disease 2019 (COVID-19) has become a pandemic with more than 2 million patients infected and a high mortality rate. NSIP pattern in a 67-year-old man undergoing pembrolizumab therapy for stage IV lung adenocarcinoma. Bronchoscopy and/or bronchoalveolar lavage are typically performed, and transbronchial biopsy can be considered at this stage. Although checkpoint inhibitor pneumonitis (CIP) has a low clinical incidence, it is likely to cause the delay or termination of immunotherapy and treatment-related death in some severe cases. OP pattern in a 51-year-old man undergoing nivolumab therapy for stage IV gastric adenocarcinoma. This immune overreaction leads to the autoimmune-type reactions observed with irAEs. Immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved outcomes in a range of malignancies but are associated with a range of potentially fatal immune-mediated toxicities such as pneumonitis. The patient previously underwent radiation therapy for multiple left posterior rib metastases. A bronchiolitis pattern may be difficult to distinguish from aspiration or infection. More severe forms of pulmonary toxicity, such as acute interstitial pneumonia leading to acute respiratory Background: Nivolumab is a novel immunotherapy that was recently approved for treatment of advanced non-small-cell lung cancer (NSCLC). GI = gastrointestinal. The results indicated the utility of a radiographic pattern–based approach as a guide for patient treatment and monitoring for immunotherapy-related pneumonitis. This article reviews the mechanism of ICIs and ICI therapy complications, with subsequent management techniques and illustrations of the various radiologic patterns of ICI–therapy related pneumonitis. AIP–ARDS pattern of pneumonitis in a 57-year-old man undergoing nivolumab therapy for stage IV lung adenocarcinoma. However, little is known about the clinical and radiological features of checkpoint inhibitor-induced lung disease. For patients with grade 2 pneumonitis, diagnostic evaluation to rule out infection may be pursued, which can include nasopharyngeal, sputum, and urine culture and sensitivity tests (27). (a) Baseline axial chest CT image shows the lungs before starting immunotherapy. 93, No. Figure 10b. (2015) Cancer immunology research. The airways are unremarkable. Radiologic response to respective treatments (ie, bronchopulmonary hygiene physical therapy and antibiotic therapy) is also often helpful. Immunotherapy was subsequently held, and steroid therapy was administered. For this journal-based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant relationships. National Institutes of Health, National Cancer Institute, Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline Summary, Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy, Ipilimumab-Induced Organizing Pneumonia on 18F-FDG PET/CT in a Patient With Malignant Melanoma, Pneumonitis Related to Melanoma Immunotherapy, PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course, A Case of Organizing Pneumonia (OP) Associated with Pembrolizumab, Lung CT: Part 2—The interstitial pneumonias: clinical, histologic, and CT manifestations, Drug-Related Pneumonitis in the Era of Precision Cancer Therapy, Bronchiolitis obliterans after combination immunotherapy with pembrolizumab and ipilimumab, Pembrolizumab-Induced Bronchiolitis in a Patient with Stage IV Non-Small Cell Lung Cancer (abstr), Radiation recall pneumonitis induced by chemotherapy after thoracic radiotherapy for lung cancer, Nivolumab-Induced Radiation Recall Pneumonitis, Nivolumab induced radiation recall pneumonitis after two years of radiotherapy, Sarcoidosis-Like Reactions Induced by Checkpoint Inhibitors, Granulomatous/sarcoid-like lesions associated with checkpoint inhibitors: a marker of therapy response in a subset of melanoma patients, Pembrolizumab-induced Sarcoid-like Reactions during Treatment of Metastatic Melanoma, PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis, Diagnosis and management of pulmonary toxicity associated with cancer immunotherapy, PD-1 inhibitor-related pneumonitis in lymphoma patients treated with single-agent pembrolizumab therapy, Open in Image Given the cytotoxic effect of conventional therapies, therapy success (for example in the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) is determined by the interval disappearance of or decrease in the size of lesions, with treatment failure suggested by increased lesion size or the appearance of new lesions (8). OP pattern in a 51-year-old man undergoing nivolumab therapy for stage IV gastric adenocarcinoma. ■ Discuss the management of irAEs and the role of the radiologist in treatment course planning in these complex cases. Several distinct radiographic patterns of pneumonitis have been observed: (a) organizing pneumonia, (b) nonspecific interstitial pneumonia, (c) hypersensitivity pneumonitis, (d) acute interstitial pneumonia–acute respiratory distress syndrome, (e) bronchiolitis, and (f) radiation recall pneumonitis. A baseline coronal chest CT image obtained before starting immunotherapy (not shown) showed no airspace abnormalities. Radiation recall is an inflammatory reaction occurring within a previously irradiated area after exposure to an inciting agent that has been observed in multiple organs and systems, including skin, lung, digestive tract, muscle, and central nervous system. Although the disruption of the immune checkpoint pathway is the principle mechanism behind stimulating immune response against tumor cells, this same pathway is also responsible for various irAEs. The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. (a) Baseline axial chest CT image shows the lungs before immunotherapy was initiated. Patient symptoms and pulse oximetry results should be closely monitored every 3 days, and if no improvement is seen 48–72 hours after starting steroid therapy, care should be escalated. HP pattern in a 52-year-old woman who underwent nivolumab therapy for stage IV lung adenocarcinoma. Figure 3c. Minimal subpleural ground-glass opacities in the right lower lobe were thought to be dependent atelectasis. Figure 10d. More invasive assessments with bronchoscopy and biopsy are generally unnecessary, particularly in lower grades, if other clinical data are suggestive of pneumonitis. Bronchiolitis pattern of pneumonitis in a 63-year-old woman undergoing nivolumab therapy for lung adenocarcinoma. Given the novel mechanism of action, the complications of these therapies have unique manifestations compared with those of conventional therapies. Furthermore, ICI therapy may also be combined with conventional chemotherapies given the ability of cytotoxic chemotherapy to potentiate the immune response of ICIs (2). Figure 10c. With conventional agents, the median time of onset of radiation recall pneumonitis after the end of radiation therapy is 95 days, although onset of 2 years after radiation therapy has been reported with nivolumab (38,41). (b) Follow-up coronal chest CT image obtained 1 month later after withholding ICI therapy and administering steroid therapy shows resolved pneumonitis, with a return to near-baseline findings. The size of the left lower lobe mass (arrow) decreased, suggesting a pseudoprogression on the previous study. (b) Follow-up axial CT image obtained 4 months later after administering nivolumab therapy shows multiple predominantly peripheral and subpleural airspace consolidative opacities (arrows), findings consistent with an OP pneumonitis pattern. Common Terminology Criteria for Adverse Events, Advances in Radiation Oncology, Vol. Illustrations show the mechanisms of action (left) of ICIs and the downstream tumor effects (right) for PD-1 and PD-L1 (a) and CTLA-4 (b) inhibitors. As OP pattern can manifest with new masslike consolidative opacities, an important differential diagnosis is progression of an underlying malignancy. (b) Axial CT image obtained 2 weeks after starting nivolumab therapy shows a region of centrilobular solid and ground-glass nodularity (black arrows) in the right lower lobe. Airspace disease can also be migratory, changing location or configuration over time (33). A bronchiolitis pattern is not a well-described pattern, only evident in one large case series and several case reports (25,36,37). Experimental Design: Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Figure 9a. ICI therapy–related pneumonitis is an uncommon although potentially serious complication of ICI therapy. Although generally considered separate from ICI therapy–related pneumonitis, sarcoidlike reaction is another potential pulmonary irAE reported with ICI therapy. 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