Search

Simple Summary: The approach to relapsed and refractory classical Hodgkin lymphoma is rapidly evolving. Over the past five years, we have seen the arrival of novel immunotherapies with impressive clinical response rates. These agents are actively being investigated earlier in the sequence of therapies and in combination with other clinically active therapies. We are also witnessing the arrival of new therapies for multiply relapsed disease such as chimeric antigen receptor T-cell therapy, which holds immense promise for patients in the future. This review aims to provide an overview of recent updates to both the standard of care and investigational approaches for patients with relapsed and refractory classical Hodgkin lymphoma. Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5–10% will have refractory disease to front-line therapy and 10–30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials. [ABSTRACT FROM AUTHOR]

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 (