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(IR)-Pneumonitis During the COVID-19 Pandemic

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(IR)-Pneumonitis During the COVID-19 Pandemic Open access Position article and guidelines J Immunother Cancer: first published as 10.1136/jitc-2020-000984 on 17 June 2020. Downloaded from Immune- related (IR)- pneumonitis during the COVID-19 pandemic: multidisciplinary recommendations for diagnosis and management 1,2 1,2 3 3 Jarushka Naidoo , Joshua E Reuss, Karthik Suresh, David Feller- Kopman, Patrick M Forde,1,2 Seema Mehta Steinke,4 Clare Rock,5 Douglas B Johnson,6 Mizuki Nishino,7 Julie R Brahmer1,2 To cite: Naidoo J, Reuss JE, ABSTRACT bronchoalveolar lavage (BAL), with the goal Suresh K, et al. Immune- Immune- related (IR)- pneumonitis is a rare and potentially of ruling out alternative diagnoses such as related (IR)- pneumonitis fatal toxicity of anti- PD(L)1 immunotherapy. Expert infection and malignant lung infiltration.3–5 during the COVID-19 guidelines for the diagnosis and management of IR- pandemic: multidisciplinary Severe acute respiratory syndrome coro- pneumonitis include multidisciplinary input from medical recommendations for diagnosis navirus 2 (SARS- CoV-2) is a newly recog- oncology, pulmonary medicine, infectious disease, and and management. Journal for nized respiratory virus responsible for the radiology specialists. Severe acute respiratory syndrome ImmunoTherapy of Cancer COVID-19 global pandemic. Since its decla- 2020;8:e000984. doi:10.1136/ coronavirus 2 is a recently recognized respiratory virus jitc-2020-000984 that is responsible for causing the COVID-19 global ration as a global pandemic by the WHO pandemic. Symptoms and imaging findings from IR- on March 11, 2020, over five million cases of Accepted 29 May 2020 pneumonitis and COVID-19 pneumonia can be similar, documented COVID-19 have been diagnosed and early COVID-19 viral testing may yield false negative worldwide, resulting in over 330,000 deaths.6 results, complicating the diagnosis and management of Importantly, patients with comorbidities such both entities. Herein, we present a set of multidisciplinary as cancer appear to have higher case- fatality consensus recommendations for the diagnosis and rates from COVID-19.7–9 Retrospective studies management of IR-pneumonitis in the setting of COVID-19 suggest patients with hematologic malignan- including: (1) isolation procedures, (2) recommended imaging and interpretation, (3) adaptations to invasive cies, lung cancer, and metastatic cancer are at particularly high risk of severe disease.10 testing, (4) adaptations to the management of IR- http://jitc.bmj.com/ pneumonitis, (5) immunosuppression for steroid-refractor y Interestingly, receipt of programmed- death 1 IR-pneumonitis, and (6) management of suspected (PD-1) pathway blockade does not appear to concurrent IR- pneumonitis and COVID-19 infection. There impact the severity of COVID-19 in patients is an emerging need for the adaptation of expert guidelines with cancer.11 That said, the diagnosis and for IR- pneumonitis in the setting of the global COVID-19 management of toxicities related to immune pandemic. We propose a multidisciplinary consensus on checkpoint blockade in the era of COVID-19 on September 30, 2021 by guest. Protected copyright. this topic, in this position paper. poses several challenges. Similar to patients who develop IR-pneumonitis, those with BACKGROUND COVID-19 infection tend to present clinically Immune- related (IR)- pneumonitis is an with fever, cough, myalgia, fatigue, and short- 12–14 uncommon but potentially fatal toxicity that ness of breath. Unlike IR- pneumonitis, occurs in 5%–10% of patients treated with however, COVID-19 is a viral illness transmis- anti- PD(L)1 immunotherapy, and is defined sible via droplet, human contact, and possibly as a focal or diffuse inflammation of the lung airborne transmission, and thus requires © Author(s) (or their parenchyma.1 Patients with IR-pneumonitis infection prevention measures to limit trans- employer(s)) 2020. Re- use most commonly present clinically with non- mission. Across the world, testing and triage permitted under CC BY-NC. No commercial re- use. See rights productive cough and shortness of breath, algorithms have been developed in order to and permissions. Published by and less commonly with fever and chest identify patients most suitable for COVID-19 BMJ. pain.2 The diagnosis of IR- pneumonitis is one testing via viral PCR assay of nasopharyngeal For numbered affiliations see of exclusion, and involves completion of a samples. In general, patients who develop end of article. standard institutional evaluation to rule out fever, respiratory changes, or other symp- Correspondence to respiratory infection inclusive of laboratory toms consistent with COVID-19 are consid- Dr Jarushka Naidoo; testing, chest CT imaging, and in selected ered for testing. Although widespread testing jnaidoo1@ jhmi. edu symptomatic cases, bronchoscopy with of asymptomatic individuals is not currently Naidoo J, et al. J Immunother Cancer 2020;8:e000984. doi:10.1136/jitc-2020-000984 1 Open access J Immunother Cancer: first published as 10.1136/jitc-2020-000984 on 17 June 2020. Downloaded from recommended, institutions may opt to test select asymp- Clinical considerations and recommendations tomatic populations such as residents of long-term care Previous to the COVID-19 pandemic, published consensus facilities or patients undergoing operative interventions. guidelines for the diagnosis and management of IR- pneu- For symptomatic patients, diagnostic evaluation with monitis had been developed by multiple oncologic soci- chest imaging (chest X- ray, CT) and other laboratory eties.3 4 17 18 We propose that selected recommendations tests (ferritin, erythrocyte sedimentation rate (ESR), within these guidelines be adapted in the context of C- reactive protein (CRP), lactate dehydrogenase (LDH), COVID-19, and outline these changes in table 1. These D- dimer, interleukin (IL)-6) are completed according to recommendations provide overall guidance in common institutional algorithms to assist in identifying cases that 15 clinical scenarios, however specific management deci- may clinically worsen, but have yet to be validated for sions should be made on a case- by- case basis, weighing their associations with clinical outcome. individual risks/benefits in the context of patient goals, Since patients with cancer have a COVID-19- related comorbidities, disease status, and provider safety. In addi- fatality rate of up to 25%,7 the timely diagnosis and tion, wherever possible, multi- specialty input should be management of this infection has rapidly risen to a 19 sought. level of equal importance as the management of these patients’ underlying cancers, and the complications of their treatment. Thus, the ability to effectively discern Isolation procedures and appropriately manage IR-pneumonitis in the context The WHO and other groups have established guide- of COVID-19 is a question of increasing clinical relevance lines for the appropriate screening and triage of 20–22 in patients with cancer, since anti- PD(L) immunotherapy patients with suspected COVID-19. When possible, is approved in 15 different cancer indications, with over routine patient visits and monitoring of otherwise clin- 40% of patients with cancer in the USA now being eligible ically asymptomatic individuals receiving cancer treat- 21 22 to receive immunotherapy in a standard of care setting.16 ments should be conducted via telemedicine. If in- person clinical evaluation is required, we recommend screening for the new onset of symptoms concerning for COVID-19 by phone prior to the scheduled visit, and METHODS again at in- person registration, to ensure patients are Recommendations: group representation and input seen in a setting where appropriate infection preven- In response to the need for clear and concise recommen- tion practices can be instituted such as a dedicated dations for the management of IR- pneumonitis in the COVID-19 assessment area. setting of the global COVID-19 pandemic, these recom- For patients who screen positive for symptoms mendations were drafted with multidisciplinary cross- concerning for IR- pneumonitis and/or COVID-19 when institutional input from medical oncology, infectious in the oncology clinic, such patients should be isolated in diseases including hospital epidemiology and infection a separate dedicated COVID-19 screening/testing area to http://jitc.bmj.com/ control, pulmonary medicine and radiology subspecial- limit exposure to other patients and healthcare workers. ists with expertise in IR- pneumonitis and COVID-19. The Specifically, this includes ensuring that the patient imme- most pressing clinically-relevant questions and recom- diately dons a face mask, and is placed in a private room mendations were discussed using an iterative, modified Delphi methodology. (ideally with negative- pressure capabilities) with the door closed. Staff assessing these patients should be trained on optimal infection prevention practices including appro- on September 30, 2021 by guest. Protected copyright. Recommendation objectives priate donning and safe doffing of personal protective The primary objectives of this position paper are to outline diagnostic evaluation and management prin- equipment (PPE) which may include a fit-tested N95 or ciples for IR- pneumonitis in the setting of COVID-19. other respirator, protective eyewear, gown and gloves. This includes emerging issues related to appropriate: Due to nationwide PPE shortages we recognize many (1) isolation procedures, (2) imaging and interpreta- facilities may not have sufficient respirators
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