Decisional Role of Interim PET in Relapsed/Refractory Classical Hodgkin Lymphoma Treated with Begev Chemotherapy As First Salvage

Achievement of complete response (CR) before autologous stem cell transplantation (ASCT) is one of the main predictive factors of outcome in patients (pts) affected by relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL) eligible to high-dose chemotherapy. The predictive role of interim PET during salvage treatment is well established in pts treated with IGEV or ICE but has not been investigated in pts receiving BEGEV (Bendamustine, Gemcitabine and Vinorelbine) as first salvage treatment.

With the aim to investigate the predictive value of PET after 2 cycles of BEGEV (PET2) in terms of CR rate and survival, we retrospectively collected data of consecutive R/R cHL pts eligible to ASCT treated from 2011 to 2021 in 3 Italian centres.

PET scans were locally evaluated using Deauville Score (DS), considering a score 1-3 negative and consistent with CR. Early relapse was defined as a relapse occurring ≤12 months from the end of first-line therapy. Survival functions were calculated from the date of initiation of BEGEV chemotherapy.

Ninety-four cHL R/R pts receiving BEGEV as first salvage therapy were included. Fifty-one (54.3%) pts were male. First-line therapy consisted in 2 to 6 ABVD chemotherapy cycles accordingly to clinical stage followed by consolidation radiotherapy (RT) in 24 (25.5%) pts. At relapse, median age was 37 years (range: 18-71 years), 51 (54.3%) pts were in stage III-IV, 16 (17%) pts had B symptoms and 34 (36.2%) pts had extranodal involvement (EI). Fifty-one (54.3%) pts were primary refractory, 23 (24.5%) pts had an early and 20 pts (21.3%) a late relapse. PET2 was performed in 86 (91.5%) pts, and resulted negative in 61 (70.9%) and positive in 25 (29.1%) pts (DS 4 in 17 and DS 5 in 8 pts). PET after 4 BEGEV cycles (PET4) was performed in 82 (87.2%) pts and resulted negative in 63 (67%) and positive in 19 (20.2%) pts (DS 4 in 10 and DS 5 in 9 pts). Complete response after 4 BEGEV was achieved in 55/61 (90.2%) PET2 negative pts and 7/25 (28%) PET2 positive pts. Considering pts evaluable for both PET2 and PET4, PET2 positive pts had a statistically lower probability to achieve CR at PET4 when compared to PET2 negative pts (Odds ratio: 0.07, CI 95%: 0.02-0.29; p<0.00001). Autologous SCT was performed in 81 (86.2%) pts, following BEGEV in 56 pts (69.1%) and after further salvage treatments in 25 (30.9%). A post-ASCT consolidation strategy was performed in 24 (29.6%) pts, and consisted in RT in 18 pts and brentuximab-vedotin in 6 pts. Ten pts received an allotransplant: in 3 cases allotransplant was planned in a tandem modality, while in 7 cases was performed after further salvage treatments for post-ASCT relapse or progression. With a median follow-up of 36.4 months (interquartile range: 20.1-50.0), 3-years overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole study population were 91.7%, 61.6% and 53.9%, respectively. No significant differences in OS were detected according to PET2 result. Conversely, both 3-years PFS and EFS were significantly superior in PET2 negative vs PET2 positive pts: 3-years PFS was 61.6% (CI 95%: 52.1-72.9) in PET2 negative and 43.6% (CI 95%: 27.9-68.4) in PET2 positive pts (p=0.0004) (Figure 1), while 3-years EFS was 71% (CI 95%: 59.8-84.3) and 23.3% (CI 95%: 11.3-48.1), (p<0.001). Univariable analysis of PFS was performed using Cox regression model and evaluating adverse risk factors at relapse (primary refractory and early relapse vs late relapse, presence of EN involvement and B-symptoms) and demonstrated a significantly inferior PFS for pts with EI (HR 1.94, CI 95% 1.01-3.74, p=0.47) and primary refractory disease or early relapse (HR 2.02, CI 95%: 1.01-4.04, p=0.047), but not for pts with B symptoms (HR 1.05, CI 95%: 0.43-2.51, p=0.9). Multivariate Cox regression model of PFS evaluating presence of EI at relapse (HR 1.55 , CI 95%: 0.74-3.25, p=0.240), time to relapse (primary refractory and early relapse vs late relapse, HR 0.84 (CI 95%: 0.36-1.96, 0.683) and PET2 result, identified PET2 positivity as the only predictive factor for PFS (HR 3.24, CI 95%: 1.55-6.77, p=0.002).

In conclusion, R/R cHL pts with PET2 positive during BEGEV salvage treatment had a lower probability to achieve CR after 2 additional BEGEV cycles and a significantly inferior PFS, and could benefit from early exposure to new therapeutic strategies before ASCT.

Rusconi:Roche: Other: congres partecipation; Takeda: Consultancy, Honoraria. Zilioli:Gilead: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: travel expenses, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: travel expenses, Speakers Bureau; Roche: Consultancy. Cairoli:Novartis, Celgene: Speakers Bureau; Gilead Sciences: Other: Travel, Accommodations; Celgene, AbbVie, Daiichi Sankyo, Novartis: Consultancy. Corradini:takeda: Honoraria; janssen: Honoraria; incyte: Honoraria; gilead: Honoraria; celgene: Honoraria; amgen: Honoraria; abbvie: Honoraria. Santoro:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Speakers Bureau; Sanofi: Consultancy; Sandoz: Speakers Bureau; Amgen: Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eli-Lilly: Speakers Bureau; Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Speakers Bureau; Abb-vie: Speakers Bureau; Incyte: Consultancy.