Cancer immunotherapy has revolutionized the practice of oncology and dramatically improved outcomes for many patients. However, like previous revolutions in cancer treatment, issues remain around the therapeutic index of this approach; how do we target effector mechanisms of immunotherapy specifically to cancer cells while leaving normal cells untouched? Even at equivalent doses of treatment, one patient might have an excellent response to therapy and no toxicity while another suffers life-threatening side-effects as his/her disease progresses inexorably. Perhaps more than any other cancer therapy, both patient- and tumor-specific factors, increasingly appreciated, determine the therapeutic index of immunotherapy.
An important aspect of this is the impact on immunotherapy of pre-treatment patient requirements for immunosuppression. In patients who require immunosuppression for pre-existing autoimmune diseases such as rheumatoid arthritis, disease responses to immunotherapy, which frequently needs to be given despite the risks of increased autoimmunity, can be blunted. Despite this, comparatively little is known about how commonly prescribed immunosuppressants modify responses to cancer immunotherapy.
A similar and frequent clinical challenge presents in patients who require immunosuppression with corticosteroids to control symptoms, for example from cerebral edema due to brain metastases. One approach in these patients is to control brain edema with asteroid-sparing agents such as bevacizumab, which is effective in reducing edema from radiation necrosis, ahead of treatment with immunotherapy. Our experience in applying this to 12 patients will be discussed, along with broader issues around the use of immunosuppression before, during and after cancer immunotherapy.