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3020 Background: Antitumor immune responses have been observed in response to ipilimumab (ipi), an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) monoclonal antibody. Per modified World Health Organization (mWHO) criteria, new lesions during cancer therapy are indicative of progressive disease (PD) and treatment failure. Final data from a single-arm, phase II study showed that ipi-treated patients (pts) with advanced melanoma who developed new lesions can go on to achieve responses with subsequent shrinkage of the new lesions. Methods: All pts were treated in study CA184008 with 10 mg/kg dosing every 3 weeks (Q3W) × 4; eligible pts received 10 mg/kg maintenance Q12W starting at Week (Wk) 24. If PD per mWHO was seen at Wk 12, ipi was withdrawn, but tumor assessments (TAs) continued in some cases for pts who were not switched to other anticancer therapies on-study, or for pts who chose to enter a roll-over study, CA184025. Immune-related response criteria (irRC) were developed based on measurements by independent radiologists. Per irRC, total tumor burden (TB, index + new lesions, when relevant) was compared at each TA to baseline measurements. irRC responses were categorized as complete or partial (irCR/PR) or stable disease (irSD25 - stable TB with > 25% reduction compared with baseline at the last TA). Results: 53/155 pts had a mWHO best overall response of PD and developed new lesions at the first TA (most at Wk 12, some earlier at an unscheduled visit). Of these, 26 were followed beyond mWHO PD at Wk 12 and 7 of these achieved irCR/PR (n = 4) or irSD25 (n = 3). Most of the irRC responders had stable or declining index lesions at Wk 12 despite new lesions. Shrinking and stabilization of new lesions was observed. This was observed in every study in which new-lesion measurements were captured. Conclusions: In pts receiving ipi, new lesions may not always indicate treatment failure, particularly in pts with decreasing or stable index lesions when new lesions appear. Shrinkage and/or eradication of new lesions after they appear has not been described in oncology. New criteria for evaluation of efficacy of ipi and related drugs are needed to fully capture clinical activity and guide treatment choices. irRC require prospective validation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb
Wolchok et al. (Tue,) studied this question.