Efficacy of Brentuximab Vedotin Maintenance Therapy Following Autologous Stem Cell Transplantation in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma with and without Pre-Transplant Exposure to Novel Agents

• Published in: Blood Vol. 142; no. Supplement 1; p. 3062
• Main Authors: Falade, Ayo S, Redd, Robert A., Shah, Harsh, Baron, Kelsey, Iyengar, Siddharth, Desai, Sanjal H., Ansell, Stephen M, Micallef, Ivana, Nedved, Adrienne, Ganesan, Nivetha, Chang, Tiffany, Shah, Gunjan L., Stuver, Robert, Moskowitz, Alison, Mei, Matthew Genyeh, Othman, Tamer, Ong, Shin Yeu, Herrera, Alex F., Armand, Philippe, Merryman, Reid W.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 02-11-2023
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-182318

Background: Maintenance therapy with brentuximab vedotin (BV) after autologous stem cell transplantation (ASCT) improved progression-free survival (PFS) among high-risk patients (pts) with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) in the phase III AETHERA trial. However, cHL treatment has changed significantly since that trial with frequent incorporation of BV and PD-1 inhibitors into earlier lines of therapy. The efficacy of BV maintenance may be different among pts who receive novel agents before ASCT.
Methods: Pts with a diagnosis of R/R cHL who underwent ASCT between 2010 and 2022 were identified at 5 US transplant centers. Pts receiving no systemic post-ASCT maintenance or BV maintenance were included, while pts receiving investigational maintenance treatments were excluded. Medical records were reviewed to identify clinical variables.
Results: 921 pts were identified. Median age was 32 yrs (IQR 24-44). 641 pts (70%) had primary refractory disease or relapsed within 12 months of frontline therapy, 326 (35%) had extranodal disease at relapse, and 173 (19%) had B symptoms at relapse. Pts received a median of 2 (1-9) lines of therapy before ASCT, including 295 (32%) who received ≥3 lines. 425 (46%) pts received BV before ASCT (including 24 pts as part of frontline treatment). 70 pts (8%) were BV-refractory (defined as failure to achieve an objective response to any BV-based treatment). 169 (18%) received a PD-1 agent with salvage treatment. 638 pts (69%) had a complete response on pre-ASCT positron emission tomography (PET). BEAM (71%) or CBV (21%) conditioning were used for most pts and 236 pts (26%) received peri-ASCT radiation.
224 pts (24%) received post-ASCT BV maintenance (including 37% of pts undergoing ASCT from 2015-2022). Compared to pts receiving no maintenance, pts receiving BV maintenance were more likely to have primary refractory/early relapsed disease (79% vs 67%, p<0.001), have received only 1 salvage regimen (79% vs 65%, p=0.001), and received BEAM conditioning (83% vs 67%, p<0.001). BV maintenance pts were less likely to receive peri-ASCT radiation (20% vs 28%, p=0.022). The median number of BV maintenance cycles was 10 (1-18) and the most common reason for discontinuation was neuropathy.
Median post-ASCT follow-up was 4.9 yrs. 5-yr PFS and OS after ASCT were 70% (95% CI 67-74%) and 85% (83-88%), respectively. Because BV-refractory pts were much less likely to receive BV maintenance (p=0.0044) and had inferior PFS (HR 2.2, p<0.001) (and therefore would serve as a confounder), we excluded BV-refractory pts from additional analyses.
Use of BV maintenance was associated with improved PFS (5-yr 81% vs 67%, HR 0.47 [0.33-0.69], p<0.001) and OS (5-yr 92% vs 83%, HR 0.38 [0.20-0.73], p=0.004). The benefit of BV maintenance depended upon pre-ASCT therapy. BV maintenance was associated with a significant improvement in PFS for pts who received no novel agents before ASCT (HR 0.41 [0.25-0.65], p<0.001), but not for BV-treated (HR 0.69 [0.38-1.25], p=0.22) or PD-1-treated pts (HR 0.63 [0.13-3.03], p=0.56) ( Figure). Among pts with 0-1 modified AETHERA risk factors, BV maintenance was not associated with a significant PFS benefit in any treatment subgroup (no novel agents, HR 0.50, p=0.087; BV-treated, HR 1.28, p=0.67; PD-1-treated, HR 2.97, p=0.44). For pts with 2+ modified AETHERA risk factors, BV maintenance significantly improved PFS in the no novel agent group (HR 0.35, p<0.001) but not in the BV-treated (HR 0.55, p=0.099) or PD-1 treated groups (HR 0.24, p=0.19). In multivariable analyses that included key variables (age, year of ASCT, conditioning regimen, peri-ASCT radiation, early relapse/primary refractory disease, B symptoms, extranodal sites, pre-ASCT PET, lines of therapy), BV maintenance was associated with a significant PFS benefit among pts who received no novel agents before ASCT (HR 0.27 [0.12-0.65], p<0.001), but not for pts treated with BV (HR 0.56 [0.28-1.10], p=0.091) or PD-1 blockade (HR 1.10 [0.22-5.56], p=0.91) before ASCT.
Conclusions: In this large cohort, BV maintenance was associated with the clearest benefit among pts who received only chemotherapy before ASCT. We were unable to identify a significant improvement in PFS for pts receiving novel agents before ASCT (which could be due to insufficient power to detect a small benefit in this population), suggesting that if these pts benefit from BV maintenance, its impact is likely more limited.
Shah:AbbVie: Membership on an entity's Board of Directors or advisory committees; Seagen Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Research Funding; BeiGene: Research Funding; ADCT: Research Funding; Epizyme: Research Funding. Desai:Seagen: Honoraria. Ansell:Takeda Pharmaceuticals USA Inc: Other: Contracted Research; Pfizer, Inc: Other: Contracted Research; Regeneron Pharmaceuticals Inc: Other: Contracted Research; Seagen Inc: Other: Contracted Research; Affirmed: Other: Contracted Research; Bristol-Myers Squibb: Other: Contracted Research; ADC Therapeutics: Other: Contracted Research. Shah:Amgen: Research Funding; Beyond Spring: Research Funding; BMS: Research Funding; ArcellX: Other: DSMB; Janssen: Research Funding. Moskowitz:Beigene: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Honoraria, Research Funding; Incyte: Research Funding; Merck: Honoraria, Research Funding; ADC Therapeutics: Research Funding. Mei:NOVARTIS: Membership on an entity's Board of Directors or advisory committees; EUSA: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Beigene: Research Funding; CTI: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Incyte: Research Funding, Speakers Bureau; SeaGen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Herrera:Merck: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; BMS: Consultancy, Other: Travel/Accommodations/Expenses, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Consultancy; Tubulis GmbH: Consultancy; AstraZeneca/MedImmune: Consultancy; Karyopharm Therapeutics: Consultancy; Regeneron: Consultancy; Kite, a Gilead Company: Research Funding; Adicet Bio: Consultancy; AbbVie: Consultancy; Allogene Therapeutics: Consultancy; Caribou Biosciences: Consultancy; Seattle Genetics: Consultancy, Research Funding; Pfizer: Consultancy; Genmab: Consultancy; Gilead Sciences: Research Funding; AstraZeneca: Research Funding. Armand:Kite - a Gilead company: Research Funding; Regeneron: Consultancy; Tessa Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Affimed Therapeutics: Research Funding; AstraZeneca: Consultancy, Research Funding; MSD: Consultancy, Research Funding; GenMab: Consultancy; Foresight Diagnostics: Consultancy; IGM: Research Funding; Xencor: Consultancy; Adaptive Biotechnologies: Research Funding; Enterome: Consultancy; Genentech/Roche: Consultancy, Research Funding; ATB Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Merck: Consultancy, Honoraria, Research Funding. Merryman:Abbvie: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Alphasights: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Research Funding.
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