Brentuximab vedotin consolidation therapy after autologous stem‐cell transplantation in patients with high‐risk Hodgkin lymphoma: Multicenter retrospective study

Abstract

The AETHERA trial reported an increased progression‐free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high‐risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real‐world patients. Seventy‐five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow‐up time was 26 months. The most common high‐risk features were primary refractory or relapsed disease <12 months (n = 61), lack of complete response (CR) to the last salvage regimen (n = 51), and having had at least two salvage regimens (n = 29). At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in 6, and SD in 3 patients), 25 had progressed. Ten died in the follow‐up, eight with progressive disease and two due to infection while in CR. The 2‐year PFS and OS rates were 67.75% (95% confidence interval [CI]: 0.55–0.77) and 87.61% (95% CI: 0.76–0.94), respectively. Seventeen patients (23%) received BV in the pre‐ASCT treatment lines, and there was no survival difference between the BV‐naïve and BV‐exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to adverse event in 12 patients. Consolidation with BV after ASCT can achieve a 2‐year PFS of 67.75% (95% CI: 0.55–0.75) with an acceptable toxicity profile.

The role of transplantation in Hodgkin lymphoma

“…There has been no OS benefit reported on the trial with significant post-protocol cross over as many patients on the placebo arm received BV after relapse. Similar results were confirmed in real-world studies as well outside of the regulated clinical trial setting calling into question the optimal timing of BV as salvage therapy before or after transplant and its role as post-transplant maintenance ( 81 , 82 ).…”

Brentuximab vedotin consolidation after autologous stem cell transplantation for Hodgkin lymphoma: A Fondazione Italiana Linfomi real‐life experience

“…BV consolidation treatment was associated with a significant reduction in the risk of progression compared to placebo, with 5‐year PFS rates of 59% and 41%, respectively, leading to BV's approval in this setting 15,16 . There are only limited real‐word data on the use of BV as post‐ASCT consolidation treatment: the French AMAHRELIS study, presented at the 2020 American Society of Hematology (ASH) congress, and a recently published Turkish experience 17,18 . It must be underlined that the AETHERA trial excluded patients who had previously received BV.…”

“… 15 , 16 There are only limited real‐word data on the use of BV as post‐ASCT consolidation treatment: the French AMAHRELIS study, presented at the 2020 American Society of Hematology (ASH) congress, and a recently published Turkish experience. 17 , 18 It must be underlined that the AETHERA trial excluded patients who had previously received BV. Based on the data emerging on BV efficacy in the salvage setting, both as a single agent and in combination with chemotherapy, an increasing number of patients now receive BV before ASCT.…”

“…recently published Turkish experience. 17,18 It must be underlined that the AETHERA trial excluded patients who had previously received BV. Based on the data emerging on BV efficacy in the salvage setting, both as a single agent and in combination with chemotherapy, an increasing number of patients now receive BV before ASCT.…”

Anti-CD30 antibody–drug conjugate therapy in lymphoma: current knowledge, remaining controversies, and future perspectives

“…Real-world data on brentuximab vedotin for cHL have demonstrated the utility and feasibility of CD30-targeted ADC therapy beyond the setting of clinical trials and specialized centers (Table 3). Although there was a paucity of data on the real-world use of brentuximab vedotin as consolidation therapy post-ASCT for some time, several recent retrospective studies have assessed the effectiveness of this approach in adults, children, and adolescents, and support the results of the AETHERA trial [50][51][52][53][54]. Real-world data also support the efficacy and acceptable safety profile of brentuximab vedotin in adults with refractory or relapsed cHL [55,56], including as a bridge to ASCT [57], and the use of brentuximab vedotin in combination with bendamustine in children, adolescents, and adults with cHL [58,59].…”