Projects

PRIA: Extracorporeal photopheresis vs. second-line immunosuppression in steroid-refractory irAE

Extracorporeal photopheresis (ECP) has been widely implemented in cancer patients, is safe and, based on its immunomodulating properties, does not negatively influence the anti-tumor response. Although ECP was initially developed in 1983 for the treatment of cutaneous T-cell lymphoma, it has shown promising efficacy in a number of other severe and difficult to treat conditions. ECP is a leukapheresisbased therapy where the patient´s blood is exposed to UV-A ex vivo after being exposed to 8-MOP (8- methoxypsoralen), which is usually well-tolerated with no reported severe grade 3-4 side effects. Based on its immunomodulating properties, we postulate that ECP is effective in treating irAE refractory to standard therapy.

  • Contribute by uploading cases of steroid-refractory irAE treated with ECP or second-line immunosuppression.

Myocarditis: Study on gene expression in irMyocarditis vs. Myocarditis of other etiology. Investigation of differences in immunophenotype; proteomics and gene expression analysis of myocardial biopsies.

  • Contribute by providing muscle biopsies. 

Encephalitis: Characterization of autoimmune encephalitis with respect to clinical presentation, response to therapy and outcome (in comparison to HSV-1 enzephalitis an anti-LGI1 enzephalitis)

IrEncephalitis is a heterogenous entity, but severe impairment of consciousness, orientation and language distinguishes it from anti-LGI1 encephalitis. CSF analysis has the highest diagnostic value in irEncephalitis, as it is abnormal in most cases and allows for exclusion of infectious origin. Early immunosuppressive treatment is essential to prevent patients from sequelae and death.

Under review.

Neurological side effects: Investigation of lymphocyte subpopulations. 

Under analysis.

Serositis: Investigation of recurring irSerositis.

Under review.

TIGER: Study to evaluate effects of immunotherapy on the coagulation (in vivo and in vitro)

FERTIM: Study to assess effects of immunotherapy on fertility.

HUNCH: Study on hematological side effects induced by checkpoint-Inhibitors

Haematological irAE (hem-irAE) are difficult to treat and have shown high mortality rates. In this study, we analysed frequency, severity and outcomes of patients who developed hem-irAE while being treated with immune checkpoint inhibitors (ICI) therapy. The patients were retrospectively identified from 18 international cancer centres. We identified 50 out of 7626 patients screened. Median onset was 6 weeks after the ICI initiation. Thrombocytopenia and leucopaenia were the most frequent hem-irAE with 34% and 34%, respectively, followed by anaemia (28%), hemophagocytic lymphohistiocytosis (4%), aplastic anaemia (2%), acquired haemophilia A (2% ) and coagulation deficiency (2% ). Other than cessation of ICI (in 60%) and corticosteroids (in 78%), treatment included second-line immunosuppression in 24% of cases. Events resolved in 78%, while 18% had persistent changes, and 2% had fatal outcomes (agranulocytosis).

Conclusion: Hem-irAE can affect all haematopoietic blood cell lineages and may persist or even be fatal. Management may require immunosuppression beyond corticosteroids. Although these irAE are rare, treating physicians should be aware, monitor blood counts regularly and promptly act upon detection.

Kramer et al., Eur J Cancer, 2021

Myositis and neuromuscular side-effects

Myositis was the most frequent neuromuscular adverse event. In 32% of cases, myositis was complicated by concomitant myocarditis. Furthermore, cases of isolated myocarditis, myasthenia gravis, polymyalgia rheumatica, radiculoneuropathy and asymptomatic creatine kinase elevation were reported. The onset of side-effects ranged from the first week of treatment to 115 weeks after the start of therapy. Most of the cases were severe (49% grade IIIeIV Common Terminology Criteria for Adverse Events), and there were two fatalities (5%) due to myositis and myositis with concomitant myocarditis. Only half of the cases (50%) completely resolved, whereas the rest was either ongoing or had sequelae. Steroids were given in 80% of the resolved cases and in 40% of the unresolved cases.

Moreira et al., Eur J Cancer, 2019