TY - JOUR
T1 - Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy
T2 - review of the literature and personalized risk-based prevention strategy
AU - Haanen, J.
AU - Ernstoff, M. S.
AU - Wang, Y.
AU - Menzies, A. M.
AU - Puzanov, I.
AU - Grivas, P.
AU - Larkin, J.
AU - Peters, S.
AU - Thompson, J. A.
AU - Obeid, M.
N1 - Publisher Copyright:
© 2020 European Society for Medical Oncology
PY - 2020/6
Y1 - 2020/6
N2 - Patients with cancer and with preexisting active autoimmune diseases (ADs) have been excluded from immunotherapy clinical trials because of concerns for high susceptibility to the development of severe adverse events resulting from exacerbation of their preexisting ADs. However, a growing body of evidence indicates that immune-checkpoint inhibitors (ICIs) may be safe and effective in this patient population. However, baseline corticosteroids and other nonselective immunosuppressants appear to negatively impact drug efficacy, whereas retrospective and case report data suggest that use of specific immunosuppressants may not have the same consequences. Therefore, we propose here a two-step strategy. First, to lower the risk of compromising ICI efficacy before their initiation, nonselective immunosuppressants could be replaced by specific selective immunosuppressant drugs following a short rotation phase. Subsequently, combining ICI with the selective immunosuppressant could prevent exacerbation of the AD. For the most common active ADs encountered in the context of cancer, we propose specific algorithms to optimize ICI therapy. These preventive strategies go beyond current practices and recommendations, and should be practiced in ICI-specialized clinics, as these require multidisciplinary teams with extensive knowledge in the field of clinical immunology and oncology. In addition, we challenge the exclusion from ICI therapy for patients with cancer and active ADs and propose the implementation of an international registry to study such novel strategies in a prospective fashion.
AB - Patients with cancer and with preexisting active autoimmune diseases (ADs) have been excluded from immunotherapy clinical trials because of concerns for high susceptibility to the development of severe adverse events resulting from exacerbation of their preexisting ADs. However, a growing body of evidence indicates that immune-checkpoint inhibitors (ICIs) may be safe and effective in this patient population. However, baseline corticosteroids and other nonselective immunosuppressants appear to negatively impact drug efficacy, whereas retrospective and case report data suggest that use of specific immunosuppressants may not have the same consequences. Therefore, we propose here a two-step strategy. First, to lower the risk of compromising ICI efficacy before their initiation, nonselective immunosuppressants could be replaced by specific selective immunosuppressant drugs following a short rotation phase. Subsequently, combining ICI with the selective immunosuppressant could prevent exacerbation of the AD. For the most common active ADs encountered in the context of cancer, we propose specific algorithms to optimize ICI therapy. These preventive strategies go beyond current practices and recommendations, and should be practiced in ICI-specialized clinics, as these require multidisciplinary teams with extensive knowledge in the field of clinical immunology and oncology. In addition, we challenge the exclusion from ICI therapy for patients with cancer and active ADs and propose the implementation of an international registry to study such novel strategies in a prospective fashion.
KW - CTLA-4
KW - autoimmune disorders
KW - checkpoint inhibitors
KW - immune-related adverse events
KW - solid organ transplantation recipients
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U2 - 10.1016/j.annonc.2020.03.285
DO - 10.1016/j.annonc.2020.03.285
M3 - Review article
C2 - 32194150
AN - SCOPUS:85083726701
SN - 0923-7534
VL - 31
SP - 724
EP - 744
JO - Annals of Oncology
JF - Annals of Oncology
IS - 6
ER -