Experience in using oncology drugs in patients with COVID-19
Authors: P. A. Ascierto
Journal: Cancer Research (2020)

In relation to the spread of severe acute respiratory syndrome coronavirus 2 (SARS CoV2), oncologists need to facesome difficult situations  First of all, safety considerations about cancer patients during this pandemia  To keep safeboth patients and healthy workers is the most important rule  In our daily practice we adopted a specific policy about the conduct of our clinical managements of melanoma patients, in order to minimise the risk of any potentialexposure  We are prioritizing patients, according to the kind of treatment and the stage of disease  In order to avoidany gathering condition which could increase the risk of infection for patients, we are optimizing access aboutadjuvant treatment, considering of high priority the higher risk patients, privileging longer infusion schedule oftreatment for immunotherapy and/or selecting patients with BRAF mutation for starting target therapy  Metastaticpatients have the highest priority, and nothing changed in their daily management except for preferring, whenpossible, the longer schedule of treatment in order to reduce the access in the hospital  The enrolment in clinicaltrials is on hold and the patients still in treatment inside clinical study are managed in the respect of GCPs as well aspossible  Some additional issues are side effects in patients on treatment with target therapy and immunotherapy  Abouttarget therapy (especially dabrafenib and trametinib), patients who develop fever higher than 37 5 without resolvingafter discontinuation, should perform COVID test before to restart the treatment  Patients on treatment with immunotherapy who show pneumonitis at CT scan (even without fever), should perform COVID test before startsteroids  Immuno-oncologists have an important experience in the management of immuno-related adverse events  Thehyperactivation of immune system due to the immunotherapy strategies can develop some conditions which need ofimmuno-suppressive drugs to reduce the harmful immune reaction  Since the acute respiratory stress syndromeCOVID-19 related seems to occur from an excess of cytokine production, we focused our attention on the cytokinesstorm which probably lead to ARDS by COVID-19 and how to prevent or treat it  We know very well the CytokineRelease Syndrome (CRS), one of the most prominent and well described toxicity from chimeric antigen receptor Tcell therapy (CAR-T), as well as from some bispecific antibodies  In particular, we know the key role played by IL-6in the pathogenesis of these kind of hyperinflammation syndromes  Considering elevated serum concentration of IL-6 and CPR in patients admitted in ICUs department, we started to use monoclonal antibodies against IL6, above all to cilizumab  In Italy we started on 19th of March a phase II study( NCT04317092 ) which enrolled 330 patients in 24 hours, with the ability of to cilizumab to reduce the one-monthmortality rate as main endpoint  Results should be reported at the end of April  Other drugs active in reducing theCRS are at moment in clinical trial or expanded access program like JAK inhibitors, complement inhibitors, toll likereceptor inhibitors and others