PD-1 Inhibitors Maintenance for cHL Post-autoHCT

Classic Hodgkin lymphoma (cHL) accounts for about 10-30% of all malignant lymphomas and predominantly occurs in individuals of working age. Thanks to modern chemoradiotherapy methods, a durable remission is achieved in 80% of patients. However, for a significant proportion of patients, achieving a sustained remission after first-line chemotherapy is not possible. The standard treatment for patients with refractory/relapsed cHL is second-line intensified chemotherapy followed by high-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT). While this approach allows some patients to achieve long-lasting remission, more than 50% of them experience disease progression or relapse. Current therapeutic strategies for such patients are limited and often fail to produce long-term remission. Given that most relapses occur within the first two years after auto-HSCT, a maintenance therapy strategy aimed at preventing relapse and disease progression is a promising avenue for improving outcomes in this patient group. In 2015, based on the results of the AETHERA study, the U.S. Food and Drug Administration (FDA) approved the use of brentuximab vedotin (BV) as consolidation therapy for patients with cHL at high risk of relapse or progression following auto-HSCT. BV demonstrated an increase in median progression-free survival (PFS), with 42.9 months in the BV group compared to 24.1 months in the placebo group. However, despite this improvement, the two-year PFS among patients receiving BV was only 63%. Moreover, in the AETHERA study, with a planned 16 cycles of BV therapy, 23% of patients discontinued maintenance therapy due to severe adverse events, and 31% required dose reductions because of peripheral neuropathy. Currently, there are data from several studies on the safety and efficacy of PD-1 inhibitor maintenance therapy for patients with cHL. In a small phase II trial, 30 patients (90% with high-risk factors) received up to 8 cycles of pembrolizumab (200 mg every 3 weeks) as maintenance therapy after auto-HSCT. The 18-month PFS rate was 82%, with an overall survival (OS) of 100% (Armand et al.). Similar results were obtained with nivolumab (240 mg every 3 weeks) as maintenance therapy. Preliminary findings showed a 6-month PFS of 92% and OS of 100%. These studies also demonstrated an acceptable toxicity profile: therapy discontinuation due to adverse events occurred in 17% of patients receiving pembrolizumab and in 10% of those on nivolumab maintenance therapy. Data have also been obtained on the efficacy of a fixed-dose nivolumab regimen (40 mg every 2 weeks) for patients with r/r cHL: the objective response rate was 70%, and the 18-month PFS was 53.6%. Based on these results, the fixed-dose 40 mg nivolumab regimen, which showed comparable efficacy for this patient group, has been included in the draft Russian clinical guidelines for the diagnosis and treatment of patients with r/r cHL. Thus, the use of PD-1 inhibitors, having a favorable toxicity profile, may achieve durable remissions in patients with cHL after auto-HSCT. Moreover, the available data indicating comparable efficacy of a fixed-dose nivolumab regimen versus the standard approach increases the accessibility of this treatment option. Employing PD-1 inhibitors is an important step in modifying the therapy strategy for patients with r/r cHL and in preventing relapses in this patient population.