Outcomes of Patients with Hodgkin Lymphoma Receiving Brentuximab Vedotin (BV) As Maintenance Therapy after ASCT According to Previous Exposure to BV. a Retrospective Analysis of the EBMT Lymphoma Working Party in Collaboration with Geltamo, FIL, Lysarc, and Turkish Lymphoma Group

Introduction: Maintenance therapy with brentuximab vedotin (BV) after autologous stem cell transplantation (ASCT) improved progression-free survival (PFS) among high-risk patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) in the phase III AETHERA trial. However, since the trial, HL treatment has evolved, often incorporating BV earlier in therapy, potentially affecting BV maintenance efficacy post-ASCT.

Methods: Information of patients with R/R HL who received BV as maintenance after first ASCT between May 2016 and January 2021 was obtained from GELTAMO, FIL, LYSARC, and Turkish Lymphoma Group databases and reported to EBMT registry. The decision to use BV consolidation was made by the attending physician on an individual basis. Patients who received BV for disease relapse after ASCT were excluded from the study. The primary endpoint was 2-year PFS from ASCT.

Results: A total of 362 patients (female 46%/male 54%) with HL met the inclusion criteria. The median age at ASCT was 31y (14-69). Among them, 159 patients (44%) had primary refractory disease, 181 (50%) relapsed within 12 months of frontline therapy, 119 (34%) had extranodal disease at relapse, 13 (8%) had bulky disease at relapse, and 50 (21%) had B symptoms at relapse. Fifty-one percent of the patients received only 1 salvage therapy before ASCT, 36% 2 lines, 12% >3, and 1% proceeded to transplant without additional treatment. A total of 187 patients (52%) received BV before ASCT; of these, 8% received BV alone and 56% received it in combination with chemotherapy (36% unknown). At the time of ASCT, 247 (72%) patients were in complete remission (CR), 72 (21%) in partial remission (PR), and 23 (7%) had refractory disease or stable disease. Median time from ASCT to BV initiation was 2.1 months (IQR 1.5-2.9). The median number of BV maintenance cycles was 12 (IQR 8-16). Twenty-seven percent of patients stopped BV maintenance due to toxicity, and 22% due to HL relapse/progression.

After a median follow-up of 2.5 years (2.2-2.6), the 2 and 5-year overall survival (OS) rates were 93.9% (95% CI 90.7-96) and 85% (95% CI 76.5-90.6), respectively, while the PFS rates were 78.1% (95% CI 73-82.4) and 69.4% (95% CI 58.6-78), respectively. In univariate analysis, relapse within 12 months of frontline therapy (HR 2.6, 95% CI 1.16-5.85, P=0.021), receiving >2 salvage therapy lines (HR 2.47, 95% CI 1.13-5.41, P=0.023), and non-CR at ASCT (HR 3.76, 95% CI 1.79-7.88, P<0.001) were associated with worse OS. Patients who had primary refractory HL (HR 1.97, 95% CI 1.24-3.13, P=0.004), and those with non-CR at ASCT (HR 3.91, 95% CI 2.42-6.33, P<0.001) had significantly lower PFS. Patients treated with BV before transplant had better 2-year OS (97.8% vs. 89.8%, HR 0.39, 95% CI 0.18-0.86, P=0.019) and 2-year PFS (83.7% vs. 72.6%, HR 0.56, 95% CI 0.35-0.9, P=0.017) than those who did not receive it. The multivariate analysis demonstrated that the only variables with a significant impact on OS were disease status at ASCT (HR 3.4, 95% CI 1.57-7.39, P=0.002) and BV treatment prior to ASCT (HR 0.41, 95% CI 0.18-0.95, P=0.037). Similarly, these two variables were the only factors significantly correlated with the PFS outcomes (HR 3.42, 95% CI 2.08-5.62, P<0.001; and HR 0.59, 95% CI 0.35-0.99, P=0.044, respectively). The aforementioned factors did not affect non-relapse mortality. Conversely, non-CR status was correlated with an elevated risk of HL relapse (HR 3.72, 95% CI 2.23-6.21, P<0.001), while BV treatment before ASCT was linked to a reduced relapse risk (HR 0.56, 95% CI 0.33-0.97, P=0.037).

Conclusions: This large EBMT-registry study shows that in patients with high-risk R/R HL receiving BV maintenance after ASCT, the factors associated with better PFS were achieving a CR before ASCT and being treated with BV before transplantation. The excellent PFS in the group of patients previously exposed to BV indicates a clear benefit of including this drug in salvage regimens prior to ASCT.