The price of tumor control

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking
antibody, has been approved for the treatment of metastatic
melanoma and induces adverse events (AE) in up to 64% of patients.
Treatment algorithms for the management of common
ipilimumab-induced AEs have lead to a reduction of morbidity, e.g.
due to bowel perforations. However, the spectrum of less common AEs
is expanding as ipilimumab is increasingly applied. Stringent
recognition and management of AEs will reduce drug-induced
morbidity and costs, and thus, positively impact the cost-benefit
ratio of the drug. To facilitate timely identification and adequate
management data on rare AEs were analyzed at 19 skin cancer
centers. Patient files (n = 752) were screened for rare
ipilimumab-associated AEs. A total of 120 AEs, some of which were
life-threatening or even fatal, were reported and summarized by
organ system describing the most instructive cases in detail.
Previously unreported AEs like drug rash with eosinophilia and
systemic symptoms (DRESS), granulomatous inflammation of the
central nervous system, and aseptic meningitis, were documented.
Obstacles included patientś delay in reporting symptoms and the
differentiation of steroid-induced from ipilimumab-induced AEs
under steroid treatment. Importantly, response rate was high in
this patient population with tumor regression in 30.9% and a tumor
control rate of 61.8% in stage IV melanoma patients despite the
fact that some patients received only two of four recommended
ipilimumab infusions. This suggests that ipilimumab-induced
antitumor responses can have an early onset and that severe
autoimmune reactions may reflect overtreatment. The wide spectrum
of ipilimumab-induced AEs demands doctor and patient awareness to
reduce morbidity and treatment costs and true ipilimumab success is
dictated by both objective tumor responses and controlling severe
side effects.