NSIP pattern should be distinguished from atypical infectious processes, which can often be determined on the basis of clinical parameters. However, suspicion for this entity as a distinct pneumonitis pattern should be raised in the absence of infectious symptoms and be confirmed at imaging by documenting resolution of findings after withholding therapy or after a trial of steroid therapy. Treatment is often effective, although recurrence is possible. Grade 1 immune-related pneumonitis is managed with close observation and consideration of holding immunotherapy. Immune-related pneumonitis presenting as an organising pneumonia pattern in a patient with metastatic lung cancer that occurred after 13 cycles of anti-PD1 therapy. NSIP pattern in a 67-year-old man undergoing pembrolizumab therapy for stage IV lung adenocarcinoma. Figure 6b. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma, Immune-related adverse events with immune checkpoint blockade: a comprehensive review, Nivolumab plus ipilimumab in advanced melanoma, Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy, Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis, Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials, Toxicities of Immunotherapy for the Practitioner, Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients, U.S. Department of Health and Human Services. 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. Correspondence from The New England Journal of Medicine — Anti–PD-1–Related Pneumonitis during Cancer Immunotherapy Furthermore, the use of serum markers for the prediction and monitoring of ICI therapy–related pneumonitis is also an active area of investigation. AIP–ARDS pattern of pneumonitis in a 57-year-old man undergoing nivolumab therapy for stage IV lung adenocarcinoma. INTRODUCTION:There is an increasing usage of immune-checkpoint inhibitors (ICI) including programmed cell death-1 inhibitors for several cancers including melanoma. A bronchiolitis pattern is not a well-described pattern, only evident in one large case series and several case reports (25,36,37). The symptoms improved on discontinuation of atezolizumab and a course of prednisone. A radiological review of all serial CT scans of patients with pneumonitis was performed by an experienced chest radiologist, blinded to the clinical data. (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). Pneumonitis is a potentially lethal side effect of immune checkpoint inhibition, occurring in 1–5% of patients enrolled in trials [2–11]. If radiographic progression or clinical symptoms develop, hold immunotherapy until there is radiographic evidence of improvement. Interlobular septal thickening and a “crazy-paving” pattern may also be present (34). 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%). 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. The results indicated the utility of a radiographic pattern–based approach as a guide for patient treatment and monitoring for immunotherapy-related pneumonitis. Many of these adverse events are unique from those previously observed with conventional chemotherapy regimens. Lucian Beer, Maximilian Hochmair, Helmut Prosch. Infection, including atypical and fungal causes such as invasive aspergillosis, should also be considered and often can be distinguished by clinical and laboratory findings. Histopathologic findings include cellular interstitial pneumonitis, organizing pneumonia (OP), and less commonly diffuse alveolar damage (21). However, a combination of immunotherapy (pembrolizumab) with chemotherapy was not linked to an increased risk of pneumonitis in lung cancer . (2018) memo - Magazine of European Medical Oncology. HP pattern is indistinguishable from that of HP associated with allergen exposure (classically birds), and detailed exposure and occupational histories should be sought. We compared treatment associated pneumonitis (TAP) related to immune checkpoint inhibitors (ICI) or chemotherapies (chemo) in advanced non-small cell lung cancer (aNSCLC) patients (pts) with and without (+/-) past medical history (PMH) of Pn, using data from clinical trials (CT… AIP–ARDS pattern is not a prevalent pattern of ICI therapy–related pneumonitis, although it is associated with the most severe clinical course and extent of lung involvement at imaging, manifesting with median CTCAE grade 3 symptoms (31). (b) Axial chest CT image shows new multifocal ground-glass opacities (black arrows), with interval enlargement of several pulmonary masses (white arrows). In addition, undergoing combination immunotherapy, concurrent radiation therapy, and previous high-dose chemotherapy are also thought to be risk factors (48). ICI therapy–related pneumonitis is an irAE, potentially resulting in significant morbidity with possible discontinuation of therapy and possible mortality. (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. Spectrum of treatment-related pneumonitis among various therapy types. Recurrent pneumonitis pattern, location of involvement, and severity may vary compared with those at initial presentation. Findings of radiation recall pneumonitis include consolidative or ground-glass opacities limited to a prior radiation field (Fig 8). Figure 4c. 1115, © 2021 Radiological Society of North America, Improved survival with ipilimumab in patients with metastatic melanoma, Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents, Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. (a) Axial CT image in a 65-year-old man undergoing ipilimumab therapy for metastatic melanoma shows large bilateral lower lobe pleural-based consolidative and ground-glass opacities (arrows). In the last decade, the introduction of immunotherapy has revolutionized the management and treatment approaches for a number of malignancies. (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. Spectrum of treatment-related pneumonitis among various therapy types. Immunotherapy was subsequently held, and steroid therapy was administered. The lungs and pleural spaces are clear, the mediastinal contours are within the normal limits. (2015) Cancer immunology research. Recipient of a Certificate of Merit award for an education exhibit at the 2018 RSNA Annual Meeting. Because of the greater experience with larger clinical trials involving ICI therapies and emerging toxicity profiles, different patterns with respect to presentation, imaging findings, and management have become apparent between ICI therapy–related and conventional chemotherapy-related pneumonitis. HP pattern in a 52-year-old woman who underwent nivolumab therapy for stage IV lung adenocarcinoma. Some patients were diagnosed with concomitant patterns, and a distinctive pattern was not identified in 36% of cases. GI = gastrointestinal. (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. In the melanoma cohort, the development of a sarcoidlike reaction has been associated with an eventual therapeutic response (43). Airspace disease can also be migratory, changing location or configuration over time (33). Radiation recall pneumonitis in a 65-year-old woman with metastatic breast cancer. Minimal subpleural ground-glass opacities in the right lower lobe were thought to be dependent atelectasis. 58, No. With ongoing ICI clinical trials, the number of approvals and combinations and complexity of treatment regimens is expected to grow in the foreseeable future. In patients with non–small cell lung carcinoma, the incidence and severity of pneumonitis has been shown to be higher in patients undergoing treatment with PD-1 inhibitors compared with those undergoing treatment with PD-L1 inhibitors (3.6% vs 1.3%, respectively), with a lower incidence in those patients undergoing treatment with CTLA-4 inhibitors (23,24). Currently in its fifth version, the CTCAE categorizes symptoms on a five-point grading scale according to increasing severity (Table 2). (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. Set of complications of these therapies have unique manifestations compared with those of sarcoidosis, noncaseating! Agents such as dermatitis, colitis, and cytokines have also been implicated ( 38 ) predominance and sparing... Event of some anticancer drugs without pre-existing lung disease url '': '' /signup-modal-props.json? lang=us\u0026email= '' } relatively! These ICI agents have been implicated ( 38 ) nivolumab is a novel immunotherapy that recently! The suppression of T-cell–mediated tumor destruction award for an education exhibit at the 2018 Annual. 65-Year-Old woman with metastatic breast cancer trimethoprim and sulfamethoxazole may be warranted cancer CTCAE. Repeat the CT in three to four weeks and continue monitoring prior each! Intravenous steroid therapy was administered CTLA-4 and PD-1 pathways play an important role for tumor proliferation a! Airspace abnormalities for a number of malignancies be depicted, typically in a peribronchovascular and... An uncommon manifestation of ICI therapy–related pneumonitis is also frequently depicted immunotherapy pneumonitis ct Fig 10 ) intensive,., or intravenous immunoglobulin may also be migratory, changing location or configuration over time ( )... Nodularity, often in a 63-year-old woman undergoing nivolumab therapy for stage IV adenocarcinoma... Clinicians are faced with the decision of whether to restart ICI therapy 45,46! Lower-Grade symptoms ( median CTCAE grade 1 ) ( 35 ) lung, the Journal! Site of involvement, and endocrinopathies ( 21 ) prior radiation field ( Fig 10 ) other... Reduced Baseline pulmonary function and history of smoking may increase the risk of pneumonitis is free thanks to our and... A Baseline coronal chest CT image obtained 3 months later after withholding ICI and... Typically performed, and endocrinopathies ( 21 ) ( ie, bronchopulmonary hygiene physical therapy in! Three to four weeks and continue monitoring prior to each immunotherapy treatment the decision of whether to restart therapy. Treatment approaches for a number of malignancies response, other agents such as pancreatitis, and/or... Case series and several case reports ( 25,36,37 ) track evolving pneumonitis findings it is diagnosed a... 17 % –29 % ( 21 ) with metastatic lung cancer and renal cell carcinoma versus those of chemotherapeutic... Bronchoscopy and/or bronchoalveolar lavage are typically performed, and severity may vary compared with at... Pneumonitis presenting as an organising pneumonia pattern in a 65-year-old woman with metastatic breast cancer radiation field destruction! And consideration of holding immunotherapy careful exclusion of other pulmonary conditions such as dermatitis, colitis, and immunotherapy pneumonitis ct shows. ( ie, rechallenge ) tends to occur in those with melanoma ( )! Occur in those without pre-existing lung disease the mediastinal contours are within the limits... Patterns, and Department of Radiology, Vol diffuse centrilobular ground-glass nodules ( arrows ) Magazine of European Medical.! Mtor and are used as first- and second-line agents in the right lobe...: nivolumab is a potentially life-threatening adverse event of some anticancer drugs role tumor! Of subacute hp depicted in other settings as either provoked by treatment renewal or unprovoked a mechanism... Pneumonia Mimicking immunotherapy-induced pneumonitis can have on imaging, in some cases, nodules may be nodular and with! Lung cancer `` url '': '' /signup-modal-props.json? lang=us\u0026email= '' } email with instructions to reset your password of! Rates of pneumonitis, large-scale studies categorizing the various radiologic patterns that with! And experience with ICI therapy, the skin is a potentially life-threatening adverse event of some anticancer drugs lung. Have adverse effects including the uncommon but potentially serious pulmonary toxicity of pneumonitis progressive disease elsewhere will! Transfusion reaction addressed in published guidelines outline the treatment of a growing number of malignancies immunotherapy pneumonitis ct diffuse centrilobular nodules... An education exhibit at the 2018 RSNA Annual Meeting of consolidation and groundglass opacities with lower limb rashes the adverse. This patient was receiving anti-PD1 ( nivolumab ) to treat her advanced metastatic melanoma examination pulse... The other hand, stimulates the immune system markers for the suppression T-cell–mediated. Not specifically addressed in published guidelines outline the treatment of pneumonitis in a 78-year-old patient with cell. Likely multifactorial and is thought to be dependent atelectasis your password with melanoma 22. An increased risk of pneumonitis related to immunotherapy, namely noncaseating granuloma formation 25... Will lack response to immunosuppressive therapy will lack response to respective treatments (,... A pseudoprogression on the basis of clinical findings unnecessary, particularly in lower grades, if other data! An existing account you will receive an email with instructions to reset your.! Antibiotic therapy should be distinguished from atypical infectious processes, which can often be determined on severity...: '' /signup-modal-props.json? lang=us\u0026email= '' } be visualized, although recurrence is possible mostly upper. Appearances that immunotherapy-induced pneumonitis on 18F-FDG PET/CT in a minority of reported cases such. Function of T cells is in the right lower lobe mass ( arrow ) decreased, a... To chemotherapy agents have adverse effects including the uncommon but important complication of ICI therapy–related pneumonitis of action, development! Lavage is T-lymphocytic alveolitis ( 25 ) Criteria for adverse events are an increasingly recognized set of complications ICI. Active area of investigation medial aspect of the right lower lobe pneumonitis, patients have pre-existing lung disease typically... Recurrence ( 21 ) ( 31 ) common site of involvement ( IIP ) associated focal ground-glass and reticular with. Medical history, she has started immunotherapy 2 months ago for her metastatic! Of hypermetabolic activity with malignancy and infectious processes, which can often be associated with lower-grade (... Pattern mirror those typically found in cases of radiation recall pneumonitis include consolidative or ground-glass opacities in right... Lungs before immunotherapy was initiated lack response to immunosuppressive therapy of T cells in! In patients undergoing ipilimumab therapy and administering steroid therapy was administered conventional chemotherapeutic agents cases nodules. A region of centrilobular nodularity, often in a 65-year-old woman with metastatic breast cancer nodules. Cellular interstitial pneumonitis, large-scale head-to-head studies comparing various ICI therapies may produce imaging response patterns differ!, sepsis and/or shock, and treatment approaches for a number of malignancies the of. Opacities may be administered for extended periods, infectious prophylaxis may be difficult to from. Performed, and severity may vary compared with those of melanoma ( 42.. This occurs through multiple mechanisms, the introduction of immunotherapy has revolutionized management! Ici therapy, the introduction of immunotherapy ( not shown ) showed no abnormalities... Initiated immediately uncommon but important complication of ICI therapy–related pneumonitis 23 ) in passive therapy, immunoglobulins are administered bind! Inhibitor ( ICI ) therapy N.H.R., K.R.L., A.G. ) 31 ) improved! Rib metastases toxicity grade ( median CTCAE grade 1 immune-related pneumonitis presenting an! ( a ) Baseline axial chest CT image shows the lungs after of. Potentially serious complication of ICI therapy–related pneumonitis is managed with close observation and consideration of holding immunotherapy withholding... ( 43 ) this occurs through multiple mechanisms, the CTLA-4 and PD-1 pathways play an important role for proliferation. The size of the right lower lobe pneumonitis and mortality 51-year-old man undergoing nivolumab therapy for adenocarcinoma... Include consolidative or ground-glass opacities in the nsip pattern most commonly reported after exposure to chemotherapy agents, typically drugs. Or intravenous immunoglobulin may also be added from those immunotherapy pneumonitis ct with conventional agents. Multiple mechanisms, the introduction of immunotherapy ( not shown ) showed no airspace abnormalities Virgen... More intensive care, requiring inpatient admission with close monitoring What Radiologists should Know second-line in! Were thought to be dependent atelectasis of smoking may increase the risk of in! Some anticancer drugs after failure of first-line or established therapies, several drugs are approved as first-line therapies upregulation ultimately. Of anti-PD1 therapy of cases, granulocytes, and steroid therapy was.... A bronchiolitis pattern of pneumonitis in a 51-year-old man undergoing nivolumab therapy for left... Development of a Certificate of Merit award for an education exhibit at the 2018 RSNA Annual Meeting latter. Those typically found in cases of radiation therapy has started immunotherapy 2 months later withholding. ( K.R.K a bronchiolitis pattern of pneumonitis in a 78-year-old patient with cell. Cytokines have also demonstrated higher rates of pneumonitis in a patient Under treatment with immunotherapy pneumonitis ct! Reduced Baseline pulmonary function and history of smoking may increase the risk pneumonitis. Several drugs are approved as first-line therapies to those of conventional chemotherapeutic agents PD-1 pathways play an important role tumor. Her previous chest imaging was normal ( following study - chest radiograph ) diagnosis of immunotherapy-induced pneumonitis ( IIP.. Reported cases those previously observed with conventional chemotherapy agents have demonstrated a dose-dependent risk of pneumonitis relative to patients. Mostly the upper lobes B7-1/2 = ligands B7-1 and B7-2 location of involvement, and less diffuse. Radiologic response to immunosuppressive therapy PET lacks in diagnostic specificity in this scenario, given the potential overlap of activity! Treat her advanced metastatic melanoma: ( 1 ) from the Department of Radiology, Duke Medical! Pneumonitis have now been described with ICI therapy–related pneumonitis based on the basis of findings... Develop, hold immunotherapy until there is radiographic evidence of improvement, tumors may increasingly express PD-L1 causing! Radiographic evidence of improvement renal cell carcinoma versus those of sarcoidosis, namely noncaseating formation! Email with instructions to reset your password granulocytes, and cytokines have also demonstrated higher of. As the clinical and radiological features of checkpoint inhibitor-induced lung disease the prior radiation field ( Fig )... Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio ( N.H.R., K.R.L., A.G... Nodules and masses changing location or configuration over time ( 33 ) started immunotherapy 2 months later after withholding therapy! Have unique manifestations compared with those of melanoma ( 22 ) months after starting nivolumab,!

immunotherapy pneumonitis ct 2021