Abstract
Background: cHL is a histopathologically distinguish cancer type with an interesting microenvironment. The number of malignant cells is small in relation to the dominant T lymphocytes that have lost their antitumor activity through different mechanisms. Therefore, reactivation of host antitumoral immune response is promising approach to convert cHL in amenable disease for the immune system. Nivolumab is a novel antibody that binds to program death receptor-1 (PD-1) and prevents immune tolerance. Recently, several published clinical trials confirmed the clinical efficacy of single agent nivolumab in patients with few cancer types. Publications on nivolumab in cHL are very scarce. The available literature is limited to only one phase 1 (Ansell et al., N Engl J Med 2015;372:311-9) and another non-randomized phase 2 (Younes et al., Clin Oncol 34, 2016 (suppl; abstr 7535) clinical study that included 23 and 80 patients with relapsed/refractory cHL respectively.
Case series: We report on three patients with heavily pretreatedcHL who failed several lines (mean 6.3, range: 3-9) of chemotherapy. Table 1 illustrates the patients' characteristics. All patients had stage IV disease at initiation of nivolumab. Two patients had very poor performance status (ECOG 3 and 4) attributed to progressivecHL and were oxygen dependent. One patient was wheelchair bound and the other was bedridden.
The patients were started on single agent nivolumab 3 mg/kg every two weeks. Impressive clinical responses were observed in all patients after just one dose of nivolumab. In particular, significant rapid clinical improvement was obtained in both patients with the worst performance status. Both patients became mobile and self-dependent within 2-4 days after the first dose. This pattern of clinical response resembles that seen on the 1stday of immune response mediated recovery from viral respiratory infection.
All patients reached complete metabolic response after 4 doses with continuous improvement of clinical condition. Both oxygen dependent patients became oxygen independent. No treatment related significant side effects were observed.
Conclusion: Pre-treatedcHL is amenable to novel immunotherapy. Nivolumab induces impressive clinical and radiological responses with excellent tolerance. The drug enriches our treatments options by reloading the immune system response against cancer. Further clinical studies are needed to determine the effectiveness on large patients' cohort.
No relevant conflicts of interest to declare.
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