key: cord-0801314-uc0hhq39 authors: O'Kelly, Brendan; McGettrick, Padraig; Angelov, Daniel; Fay, Michael; McGinty, Tara; Cotter, Aoife G.; Sheehan, Gerard; Lambert, John S. title: Outcome of a patient with refractory Hodgkin lymphoma on pembrolizumab, infected with SARS‐CoV‐2 date: 2020-05-25 journal: Br J Haematol DOI: 10.1111/bjh.16798 sha: 68a72f62266b88445d45dc2850b4cceec46ef95b doc_id: 801314 cord_uid: uc0hhq39 A 22-year-old female presented the Emergency Department on the 14th March 2020 with a 3 day history of cough, pyrexia, sore throat, chills and rigors. Dyspnoea, myalgia, anosmia did not feature at presentation. The patient had a history of early-stage unfavourable-risk, classical Hodgkin Lymphoma (HL) for which she was diagnosed in May 2017. She underwent two cycles of adriamycin/bleomycin/vinblastine/dacarbazine (ABVD) with escalation to bleomycin/etoposide/adriamycin/cyclophosphamide/vincristine/procarbazine/prednisolone (escBEACOPP) for four cycles due to a suboptimal response on interval positron emission tomography (PET) scan. Within the first six days of stay the patient was pyrexial and had rising O 2 requirements. Shortness of breath coincided with bi-basal crackles on auscultation of lung fields and evolving infiltrates in the lower zones bilaterally on chest X-rays (Fig 1) . Supplementary oxygen requirements increased from 0% on day 1 to a fraction of inspired oxygen (FiO 2 ) of 40% on day 6. The intensive care service was consulted but intubation was not required at this time. Therapy was not altered throughout this period until day 7 (Day 6 of LPV/r) with the development of new diarrhoea. Antibiotics and LPV/r were stopped. At that time the patient was switched to hydroxychloroquine (HCQ) and azithromycin. The patient remained febrile until day 13 of symptoms (day 10 of admission and day 2 of HCQ/azithromycin). Corticosteroids were decided against. A drop in CRP levels, improvement in oxygenation, and resolution of symptoms appeared to coincide with commencement of HCQ and azithromycin (Fig 2) . The patient was well, apyrexial and had no supplemental O 2 requirements at time of discharge on day 16 of symptoms (day 13 of admission). Reports of outcomes for patients living with malignancy who are infected with SARS-CoV-2 are limited but appear to be worse than for the standard population. In a prospective cohort study of 1 590 Chinese patients diagnosed with COVID-19, 1% were found to have a history of cancer. 1 These patients, especially the majority who had lung cancer, had a higher risk of severe events, a composite end-point of admission to intensive care unit, intubation and death, compared to the reminder of the cohort (39% vs. 8%, P = 0Á0003). Furthermore a report from a single centre in Wuhan indicated that people living with cancer were more likely to acquire COVID-19 infection than the general population [heart rate (HR) 2Á31, 95% confidence interval (CI) 1Á89-3Á02] potentially due to the frequency of interactions with a healthcare setting. 2 Our patient developed symptoms consistent with pneumonitis, a known complication in up to 2Á5% of those receiving PD-1 inhibitors. 3 At the time of presentation levels of community transmission of COVID-19 were low in the Republic of Ireland with 90 cases and an incidence of 1Á9 per 100,000 population. Despite this a decision was made to test for SARS-CoV-2 as the primary differential. correspondence Pembrolizumab is an immune checkpoint inhibitor targeting programmed cell death 1 (PD-1) ligand, used in melanoma, non-small cell lung cancer, urothelial cancer, and refractory HL. Predisposition to serious infection is not a feature of the monoclonal antibody, in fact the adverse appears to be true even relative to other immune checkpoint inhibitors. 4 Patients receiving pembrolizumab have been shown to have increased levels of seroconversion with influenza vaccination compared to standard population. 5 It is unknown to what extent pembrolizumab can potentiate immunological response in those with COVID-19. Bersanelli et al. hypothesise the potential dangers of administering PD-1 inhibitors in this context, the potential for dual pathology for lung injury, cytokine release syndrome caused by PD-1 inhibitors, overactivation of T cells, and mononuclear predominance in acute respiratory distress syndromeassociated COVID-19 may lead to a synergistic pro-inflammatory state. 6 We report a positive outcome in a patient with refractory HL albeit with prolonged fevers and symptomatology and raised inflammatory markers in the context of HL and approaching her seventh cycle of pembrolizumab. Our Correspondence patient was pyrexial for 13 days, longer than the median of 10 (95% CI 8-12 days) reported elsewhere. 7 Factors in this patient's disease course may be underlying malignancy, significant exposure to cytotoxic chemotherapy, waning levels of pembrolizumab with dissipation of immune activation, a change of viral-directed therapy from LPV/r to HCQ and azithromycin or the natural progression of a new infectious disease. We highlight that this report is limited, being a single case. The patient had a number of factors associated with favourable outcome in COVID-19, younger age, female sex, and no other significant comorbidities like diabetes mellitus, obesity, or cardiovascular disease. We would also like to highlight potential dilemma of an acute respiratory presentation in the current climate in patients taking PD-1 inhibitors. Pembrolizumab-induced pneumonitis, although a rare complication, carries a high mortality. While prompt administration of corticosteroids is necessary in the case of pembrolizumab-induced pneumonitis, this strategy may result in worse outcomes in patients affected by COVID-19. 8 A careful risk versus benefit assessment using a multidisciplinary approach is advised in these cases. The authors received no funding for the preparation of this manuscript. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China Transmission in patients with cancer at a tertiary care hospital in Wuhan, China Clinical characteristics and treatment of immune-related adverse events of immune checkpoint inhibitors The spectrum of serious infections among patients receiving immune checkpoint blockade for the treatment of melanoma. Clinical Infectious Diseases Immunological insights on influenza infection and vaccination during immune checkpoint blockade in cancer patients Controversies about COVID-19 and anticancer treatment with immune checkpoint inhibitors Clinical progression of patients with COVID-19 in Shanghai Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury The authors declare to have no conflicts of interest to declare regarding the present work. Patient consent was obtained for submission. All authors contributed to the writing of this article.