Symposium | Targeted therapies for classic Hodgkin lymphoma

During the European School of Haematalogy (ESH) 4th How to Diagnose and Treat Lymphoma Conference, the Lymphoma Hub held a symposium on November 2, 2024, titled, Treating classic Hodgkin lymphoma (cHL): Spotlight on targeted therapies. Here, we share a presentation by Anna LaCasce, Harvard Medical School, Boston, US, discussing the current landscape of targeted therapies for cHL.

LaCasce begins by highlighting key molecular targets for the treatment of cHL, such as CD30 and PD-1 (Figure 1).¹ She discusses approved therapies targeting these pathways, including brentuximab vedotin for CD30, and checkpoint inhibitors nivolumab and pembrolizumab for PD-1, along with their clinical indications (Figure 2). 

Figure 1. Key cellular targets in the treatment of cHL* 

CAR, chimeric antigen receptor; CD, cluster of differentiation; cHL, classic Hodgkin lymphoma; PD-1, programmed death 1.
*Adapted from Wu, et al.¹ Created using Biorender.com.

Figure 2. Overview of approved targeted therapies for cHL 

ASCT, autologous stem cell transplant; auto-HSCT, autologous hematopoietic stem cell transplantation; CD, cluster of differentiation; cHL, classic HL; HL, Hodgkin lymphoma; PD-1, programmed death 1; R/R relapsed/refractory.

LaCasce provides an overview of the key clinical trials and their outcomes for approved targeted therapies in cHL:

Brentuximab vedotin (BV)

• The pivotal phase II trial (NCT00848926) of BV in heavily pre-treated patients with cHL showed an overall response rate (ORR) of 75%, with about a third of patients achieving a complete remission (CR). Peripheral sensory neuropathy was the most common adverse event (AE) and tended to improve over time after the completion of therapy. 
• The phase III AETHERA trial (NCT01100502) evaluated BV as a maintenance therapy after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with high-risk relapse disease. The 5-year progression-free survival (PFS) in the BV arm was 59% compared with 41% in the placebo arm, with patients having ≥3 risk factors benefiting the most.
• The phase III ECHELON-1 trial (NCT01712490) evaluated BV + AVD (doxorubicin, vinblastine, and dacarbazine) vs bleomycin + AVD (ABVD) in patients with Stage 3 or 4 cHL. Modified PFS improved by 4% in the BV+AVD arm vs ABVD arm, with this survival benefit sustained over 5 years of follow-up and observed in both PET-positive and -negative patients.
• The phase III AHOD1331 trial (NCT02166463) evaluated BV + standard chemotherapy in pediatric patients with cHL, aged 2–21 years. The 3-year PFS and OS rates with BV were 92.1% and 99.3%, respectively, compared with 82.5 and 98.5% with standard care.
• The phase III HD-21 trial (NCT02661503) evaluated BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) vs escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with newly diagnosed, advanced-stage, PET-2-positive cHL. The 4-year PFS rates in the BrECADD arm were 94.3%, the highest ever reported in clinical trials in patients with newly diagnosed, advanced-stage, PET-2-positive cHL, compared with 90.9% in the escalated BEACOPP.

Nivolumab

• The phase I/II CHECKMATE 039 trial (NCT01592370) showed that nivolumab had a manageable safety profile and an ORR of >80% in patients with previously heavily treated R/R cHL.
• The phase II CHECKMATE 205 trial (NCT02181738) showed that nivolumab exhibited durable responses, particularly in a subset achieving CR, and a manageable safety profile in patients with R/R cHL following auto-HSCT.
• The phase III SWOGS1826 trial (NCT03907488) evaluating nivolumab + AVD vs BV + AVD in newly diagnosed patients with advanced stage cHL showed a 2-year PFS of 92% vs 83%, respectively. The safety profile was more favorable with nivolumab + AVD compared with BV + AVD.

Pembrolizumab

• The phase III KEYNOTE-204 (NCT02684292) compared pembrolizumab and BV in patients with R/R cHL who had relapsed following auto-HSCT or were not eligible for auto-HSCT. The median PFS was 13.2 months with pembrolizumab vs 8.3 months with BV.
• The phase II KEYNOTE-087 trial (NCT02453594) evaluating pembrolizumab monotherapy in patients with R/R cHL showed durable response, particularly in a subset achieving CR.

This independent educational activity was supported by Takeda. All content was developed independently by the faculty in collaboration with SES. The funder was allowed no influence on the content of the symposium.