key: cord-353939-vz2bpkyk
authors: Ranger, Amita; Haji, Ruby; Kaczmarski, Richard; Danga, Akila
title: Interleukin‐6 Blockade Treatment for COVID‐19 associated Cytokine Release Syndrome in a Patient with Poorly Controlled Chronic Myeloid Leukaemia
date: 2020-06-01
journal: Br J Haematol
DOI: 10.1111/bjh.16901
sha: 
doc_id: 353939
cord_uid: vz2bpkyk

In December 2019, a novel coronavirus pneumonia, coronavirus disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) was reported in Wuhan, China. A hyperinflammatory immune response, or cytokine release syndrome (CRS) is observed in critically unwell patients with SARS‐CoV‐2 globally. Severe lymphopenia, hyperactivated pro‐inflammatory T cells(1) and decreased regulatory T cells(2) are seen in these critically ill patients, suggesting dysregulated immune responses.

This article is protected by copyright. All rights reserved hyperferritinaemia and an elevated C-Reactive Protein (CRP). Early identification and management of COVID-19 induced CRS has the potential to minimise morbidity and mortality.

Tocilizumab, a humanised, monoclonal antibody against soluble and membrane interleukin-6 receptors (IL-6R), blocks IL-6 signalling and reduces inflammation. It is licenced in the management of rheumatoid arthritis and CAR-T cell associated CRS.

There have been published case series and reports of the successful treatment of COVID-19 induced CRS with Tocilizumab 4-6 . There is limited, high quality data on the outcomes of Tocilizumab in this setting and this is being addressed in the RECOVERY trial 7 . We describe our experience of the successful treatment of a patient with chronic myeloid leukaemia (CML) and COVID-19 associated CRS with Tocilizumab in a district general hospital setting.

A 52-year-old Indian man with poorly controlled CML, despite compliance with the tyrosine kinase inhibitor (TKi) Imatinib, attended for outpatient review. In view of poor haematological response, Imatinib was discontinued and he was asked to start hydroxycarbamide cytoreduction pending results of tyrosine kinase domain mutation analysis. He reported fevers, which had started 3 days earlier. An infection screen was performed including testing for COVID-19. He was prescribed oral antibiotics and advised 

This article is protected by copyright. All rights reserved our patient was made and granted. On day 12 of symptom onset, he received 600mg

Tocilizumab intravenously, in-line with the RECOVERY trial dosing protocol. There was rapid cessation of his fevers and a significant reduction in his inflammatory markers within 24 hours of Tocilizumab therapy (Figure 2) . A consistent improvement in his oxygen requirements was observed and he was weaned off CPAP on day 16 with discontinuation of supplementary oxygen therapy on day 19 of his illness.

Critical care beds are a limited resource and patients with haematological disorders are considered to have poor outcomes following admission to intensive care units (ICU).

Despite overall improved outcomes in haematology patients 8 We describe the successful treatment of COVID-19 associated CRS with Tocilizumab in a patient with an uncontrolled haematological malignancy. Equality in access to investigational therapies should be actively pursued, especially in disadvantaged patient Accepted Article cohorts, and can be achieved outside of tertiary referral centres and the clinical trials process. Therapies such as this have the potential to change the outcome of severe COVID-19 infection and prevent ICU admission, particularly in patients believed to be unsuitable for critical care or where there is a great demand on critical care resources. 

This article is protected by copyright. All rights reserved symptom onset. Following Tocilizumab therapy there was rapid cessation of his fevers and improvement in his ferritin and CRP. There followed a consistent improvement in his respiratory parameters. The on-going elevation in the D-Dimer is likely to represent the complex COVID-19 associated hypercoaguable state.

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Dysregulation of immune response in patients with COVID-19 in Wuhan, China

IL-6 in inflammation, immunity, and disease

First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab

Tocilizumab treatment in COVID-19: A single center experience

Interleukin 6-blockade treatment for severe COVID-19 in two patients with multiple myeloma

Can we still refuse ICU admission of patients with hematological malignancies?

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis

Accepted Article