A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma

Simple Summary Relapsed or refractory classical Hodgkin lymphoma remains a difficult treatment challenge. Despite responses with the checkpoint inhibitors nivolumab and pembrolizumab, patients eventually progress. Combining other treatments with checkpoint inhibitors may provide more frequent and durable responses in this setting. We conducted a phase II study in relapsed or refractory Hodgkin lymphoma combining nivolumab with the Bruton's tyrosine kinase inhibitor ibrutinib. Although we did not find an increase in the response rate of this combination compared to that previously reported, responses tended to be durable even in patients who progressed on nivolumab therapy prior to enrollment. Larger studies combining Bruton's tyrosine kinase inhibitors with checkpoint blockade are warranted, especially in patients who had progressed previously on checkpoint inhibitor therapy. Background: Relapsed or refractory classical Hodgkin lymphoma (cHL) remains a difficult treatment challenge. Although checkpoint inhibitors (CPI) have provided clinical benefit for these patients, responses are generally not durable, and progression eventually occurs. Discovering combination therapies which maximize the immune response of CPI therapy may overcome this limitation. We hypothesized that adding ibrutinib to nivolumab will lead to deeper and more durable responses in cHL by promoting a more favorable immune microenvironment leading to enhanced T-cell-mediated anti-lymphoma responses. Methods: We conducted a single arm, phase II clinical trial testing the efficacy of nivolumab in combination with ibrutinib in patients >= 18 years of age with histologically confirmed cHL who had received at least one prior line of therapy. Prior treatment with CPIs was allowed. Ibrutinib was administered at 560 mg daily until progression in combination with nivolumab 3 mg/kg IV every 3 weeks for up to 16 cycles. The primary objective was complete response rate (CRR) assessed per Lugano criteria. Secondary objectives included overall response rate (ORR), safety, progression free survival (PFS), and duration of response (DoR). Results: A total of 17 patients from two academic centers were enrolled. The median age of all patients was 40 (range 20-84). The median number of prior lines of treatment was five (range 1-8), including 10 patients (58.8%) who had progressed on prior nivolumab therapy. Most treatment related events were mild (更多