To treat or not to treat: Patient exclusion in immune oncology clinical trials due to preexisting autoimmune disease

Abstract

Newly developed immune checkpoint inhibitors (ICIs) demonstrate impressive clinical activity. However, they can also cause life‐threatening side effects. The efficacy and toxicity associated with ICIs both derive from unregulated, enhanced immune activation. Health care providers have been hesitant to prescribe these medications to patients who have preexisting autoimmune disease (AD) because of concerns that this may exacerbate their underlying immune condition. These patients have also been excluded from ongoing ICI clinical trials. However, new data suggest that the potential benefits of ICI treatment may outweigh the potential risks for this patient group as long as physicians also provide sufficient monitoring for AD exacerbations or other side effects. Therefore, it may be appropriate to include patients with advanced malignancies and preexisting AD in ICI clinical trials when no other effective cancer treatment options exist. Overall, physicians should avoid excluding patients from ICI therapy unnecessarily when the potential benefits outweigh the potential risks.

Cancer as a System Dysfunction

“…Figure 6 compares the level of autoimmune response for the two immunotherapy options. Consistent with previous experience [21], our model indicates that non-specific therapies may create greater risk for autoimmune disorders than targeted therapies. The autoimmune impact of targeted immunotherapies is much lower, as they are intended to raise the productivity of targeted cells, rather than the overall population of immune system cells.…”

Association of immune-related adverse events induced by nivolumab with a battery of autoantibodies

“…On the other hand, we did not observe the same favourable association between autoantibody positivity and cancer-related outcomes. Unlike the exclusion criteria applied in most clinical trials [ 8 ], selected patients with autoimmune features could be suitable candidates for receiving ICIs, especially if we apply tools capable of detecting individuals with a problematic risk-benefit ratio. There is still a need to improve our understanding of the relationship among autoimmunity profile, risk of irAEs and ICI efficacy [ 30 ].…”

“…Concerning toxicity, though many patients receiving ICIs experience some form of irAEs, which hinder or even prevent ICI administration, predictors of irAEs are not well established [ 6 ]. On the other hand, patients diagnosed with autoimmune diseases, some of which are per se risk factors for malignancy [ 7 ], have been systematically excluded from the pivotal clinical trials relating to ICIs [ 8 ]. Despite this hampering access to ICIs, the available evidence indicates that survival is better in patients who experience irAEs than those who do not [ 9 ].…”

Melanoma and Vitiligo: In Good Company

“…Considering the previously reported data, pre-existence in a patient of an autoimmune disease could be a possible obstacle in the prescription of check-point inhibitor immunotherapy. However, new data suggest that benefits from immunotherapy treatments may outweigh the exacerbation of pre-existing autoimmune disease, especially when the pathology taken into account is not a life-threatening disease such as leukoderma [81].…”