- ICI (immune checkpoint inhibitors) and immunocompetence.
- Hematological irAEs (immune related adverse event) are uncommon, as ICI secondary autoimmune thrombocytopenia and neutropenia, antibody-mediated hemolytic anemia and thrombotic thrombocytopenic purpura are rare.
- Their impact may actually be beneficial in countering the tumoral immunosuppressive microenvironment.
- Considering the potential anti-PD1/PD-L1 pneumological toxicity.
- As already known, the presence of an underlying lung disease, particularly interstitial pneumopathies, is considered a major risk factor for developing ICI related pneumonitis, which is mostly seen with the use of anti-PD1/PD-L1.
- Synergy between SARS-CoV-2 (characterized by interstitial pneumonitis) and anti-PD1/PD-L1 related pneumonitis, despite only hypothetical, cannot be surely ruled out.
- Regarding the Cytokine Release Syndrome (CRS).
- CRS is an immune hyperactivation phenomenon, mostly seen with T cell-engaging immunotherapy (CAR-T, anti-PD1/PD-L1). It is characterized by high levels of IL-6, IFN- γ and other cytokines, leading to fever, malaise, myalgias and possibly to severe organ toxicity and death.
- One of the most important mechanism underlying the deterioration of disease in COVID-19 is represented by a cytokine storm leading the ARDS or multiple organ failure. Cytometric analyses and pathological findings associated with ARDS in COVID-19 patients suggest that an overactivation of T-cells may contribute to this severe immune lung injury.
- Therefore, the hypothesis of a synergy between ICI related CRS and COVID-19 pathogenesis cannot be excluded.
- As most irAEs occur in the first 6 months of treatment, it would be reasonable to proceed with certain caution with ICI administration for those initiating therapy or in their first months of treatment.
- ICI-related pneumonitis ranges from 2.5-5% with anti-PD-1/PD-L1 monotherapy and ICI-induced CRS is quite rare. Therefore, those hypothetical dangers should not prevent oncologists from offering a potentially curative and often well-tolerated treatment, particularly for highly responsive diseases, but definitely warrants a follow up.
- Tocilizumab (monoclonal antibody that binds the human IL-6 receptor, inhibiting its signal transduction), which is currently used for rheumatoid arthritis, is currently in investigation as a possible treatment for ICI immune toxicity and also for SARS-CoV-2 infection.
This information comes from an opinion article written by Dr. Melissa Bersanelli, an oncologist working in Italy. Tocilizumab is currently being investigated as a potential treatment in three clinical trials in China and Italy and will be investigated in 7 more clinical trials (clinicaltrials.gov, using “tocilizumab” and “covid-19” for research on the April 1st, 2020).
- Bersanelli M. (March 26, 2020). Controversies about COVID-19 and anticancer treatment with immune checkpoint inhibitors. Immunotherapy. https://doi.org/10.2217/imt-2020-0067
- Kattan J., Kattan C., Assi T. (April 14, 2020). Do Checkpoint inhibitors compromise the cancer patient’s immunity and increase the vulnerability to COVID-19 infection? Future Medicine. https://doi.org/10.2217/imt-2020-0077