Pembrolizumab Consolidation Active in Hodgkin Lymphoma Posttransplant

For patients with relapsed/refractory classical Hodgkin lymphoma who responded to salvage chemotherapy, autologous stem cell transplant (ASCT) remains the gold standard of treatment. While this may result in cure for some patients, up to half will relapse, and treatments following relapse are associated with short survival. However, results from a phase III AETHERA study demonstrated that consolidation therapy with brentuximab vedotin after ASCT may increase the chance of cure for patients with high risk for relapse. These results led to approval of brentuximab vedotin for maintenance therapy after ASCT for high-risk patients, but more options are needed.

Classical Hodgkin lymphoma is a uniquely immunosensitive malignancy, and use of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis has been shown to have a strong antitumor effect with objective response rate around 70% in patients who relapsed after or were ineligible for ASCT. In a cohort of 30 patients with relapsed/refractory classical Hodgkin lymphoma included in multi-cohort phase II trial, use of consolidation therapy with the PD-1 inhibitor pembrolizumab (200 mg intravenously every 3 weeks up to 8 cycles) following salvage chemotherapy and ASCT was examined as a potential method to improve outcomes posttransplant.

The majority (87%) of the patients had high-risk disease (primary refractory disease, relapse within 12 months, or extranodal disease at relapse). Six patients (20%) had received a PD-1 inhibitor as a salvage therapy. All but two patients were in complete remission (CR) following ASCT, and these two patients achieved CR after 3 cycles of pembrolizumab. At 19 months, only 5 patients had progressed, and 81% of patients remained in CR. The estimated progression-free survival (PFS) at 18 months was 82%. The PFS rate was consistent regardless of risk factors, and the 19-month PFS among high-risk patients was 85%. All patients remained alive at 19 months.

The adverse event (AE) profile was manageable and consistent with the known safety profile of pembrolizumab. Grade 3/4 AEs occurred in 40% of patients. Immune-related (ir)AEs occurred in 43% of patients, with grade 2 or 3 pneumonitis and cough as the most common irAE. There were no grade 4 irAEs or treatment-related deaths. Five patients discontinued treatment due to AEs. Importantly, pembrolizumab did not significantly disturb the immune constitution of patients after ASCT. Moreover, there was a trend towards an earlier NK cell recovery that may be important for the antitumor activity of PD-1 blockade.

The investigators concluded that data from this small study indicate the safety and efficacy of pembrolizumab as consolidation therapy post-ASCT for patients with relapsed/refractory classical Hodgkin lymphoma. While crosstrial comparisons are difficult, the 19-month PFS of 85% seen with pembrolizumab in high-risk patients compares favorably to the approximately 70% PFS rate seen with brentuximab vedontin and 45% with placebo in the ATHERA trial and support further investigation of PD-1 consolidation, including in combination with brentuximab vedotin.

Blood. 2019 April 4. [Epub ahead of print.]
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