PD-1 Inhibition in Hodgkin's Lymphoma

PD-L1 is upregulated in Hodgkin’s lymphoma, causing an inflammatory response with T-cells, B-cells, and monocytes. To counter this, some of the more revolutionary therapies currently being explored for patients with Hodgkin’s lymphoma involve PD-1 blockade, says Ivan Marques Borrello, MD. A number of anti-PD-1 monoclonal antibodies are currently being explored, including nivolumab, pembrolizumab, and pidilizumab. At the 2014 ASH Annual Meeting, promising findings from separate early phase trials were presented for pembrolizumab and nivolumab in patients with classifcal Hodgkin lymphoma (cHL), with similar efficacy in each study, Borrello suggests.

In a phase II study, treatment with the PD-1 inhibitor pembrolizumab generated responses in 66% of patients with heavily pretreated cHL (>4 prior therapies). Of the 29 evaluable patients with cHL who received pembrolizumab, six patients (21%) experienced complete remission while 13 patients (45%) achieved a partial remission. Among those who had previously failed transplant, the ORR reached 75% and four of these patients achieved a complete remission.

In a small phase I trial, nivolumab demonstrated an overall response rate of 87% in pretreated patients with cHL. Among the 18 patients who had previously failed brentuximab vedotin, the ORR was 89%, with 6% achieving complete response and 83% partial response. The PFS rate at 24 weeks was 86% (95% CI, 62-95%). Median overall survival has not been reached.

Evidence has shown that individuals with high PD-L1 expression tend to respond better to these therapies. PD-1 blockade may serve as a bridge for patients to receive allogeneic transplant, which may ultimately be curative, states Borrello. Achieving high response rates has a greater socioeconomic impact in diseases, such as Hodgkin’s lymphoma, that affect younger individuals, adds Borrello.