Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma

Abstract

In this phase 1/2 study, brentuximab vedotin (BV) and nivolumab (Nivo) administered in combination were evaluated as initial salvage therapy in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). Patients received up to 4 cycles of combination treatment, with BV administered on day 1 and Nivo on day 8 of the first cycle. For cycles 2 to 4, BV and Nivo were both administered on day 1. After study treatment, responses were evaluated by investigators per the 2014 Lugano classification, and patients could proceed to autologous stem cell transplantation (ASCT). Sixty-two patients were enrolled; the complete response rate among all treated patients (n = 61) was 61%, with an objective response rate of 82%. Before ASCT, adverse events (AEs) occurred in 98% of patients, mostly grades 1 and 2. Infusion-related reactions (IRRs) occurred in 44% of patients overall, with 41% of patients experiencing an IRR during at least 1 infusion of BV. Five patients (8%) were treated with systemic steroids for immune-related AEs. A reduction of peripheral T-cell subsets including regulatory T cells was observed after the first dose of BV, and reduced serum levels of thymus- and activation-regulated chemokine concurrent with an increase in proinflammatory cytokines and chemokines were seen after the first BV plus Nivo infusions. The combination of BV plus Nivo was an active and well-tolerated first salvage regimen, potentially providing patients with R/R HL an alternative to traditional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02572167.

Checkpoint Inhibition in Hodgkin Lymphoma - a Review

“…Various clinical trials are currently ongoing to evaluate the efficacy and safety of such combinatory approaches, also in patients with cHL. Early results of 62 patients with r/r cHL treated with BV and nivolumab in a phase I/II study reported an ORR 85% with a 64% CRR and irAEs °3 occurring in < 5% of patients [47]. Similar results were also observed among 19 patients treated with the same combination in another phase I trial (ORR 89%, CRR 50%), with 2 (10.5%) cases of severe pneumonitis observed [48].…”

The treatment of older Hodgkin lymphoma patients

“…Consequently, antibodies against PD‐1 have shown remarkable efficacy in relapsed/refractory HL and compounds, such as nivolumab and pembrolizumab, are therefore likely candidates for older patients (Ansell et al , ; Younes et al , ; Chen et al , ). Although, again, trials testing nivolumab and pembrolizumab included only a few older patients, the antibodies had little toxicity compared to chemotherapy, and trials testing combinations brentuximab vedotin and nivolumab are currently recruiting (Herrera et al , ).…”

The role of transplantation in Hodgkin lymphoma

“…Moreover, anti‐PD1 agents may enhance the response rates of pre‐ASCT single‐agent BV, as documented in earlier trials (Chen et al , 2015a; Moskowitz et al , 2015a). Herrera et al () conducted a phase 1/2 trial of BV in combination with nivolumab (Nivo‐BV) in patients with relapsed and refractory HL failing induction therapy. BV was delivered at the standard dose of 1·8 mg/kg on day 1 and nivolumab was given at the dose of 3·0 mg/kg (on day 8 on cycle 1, then on day 1); each cycle was repeated every 21 days, for up to 4 cycles.…”