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Stage IIB Hodgkin lymphoma (HL) patients, with a mediastinum-to-thorax (M/T) ratio of ≥0.33 or extranodal localization have a poor prognosis and are treated either as limited or advanced stage. We compared these two approaches in patients included in two randomized phase III trials enrolling previously untreated early (H10) or advanced stage HL (AHL2011). We included HL patients with Ann-Arbor stage IIB with M/T ≥0.33 or extranodal involvement enrolled in the H10 or AHL2011 trials with available PET at baseline and after two cycles of chemotherapy (PET2). Baseline total metabolic tumor volume (TMTV) was calculated using the 41% SUVmax method. PET2 response assessment used the Deauville score. 148 patients were eligible, including 83 enrolled in the AHL2011 trial and 65 in the H10 trial. The median TMTV value was 155.5 mL (8.3-782.9), 165.6 mL in AHL2011 and 147 mL in H10. PET2 positivity rates were 16.9% (n=14) and 9.2% (n=6) in AHL2011 and H10 patients, respectively. With a median follow-up of 4.1 years (95%CI 3.9-4.4), overall 4-year PFS was 88.0%, 87.0% in AHL2011 and 89.2% in H10. In univariate and mutivariate analyses, baseline TMTV and PET2 response influenced significantly PFS (HR=4.94, HR=3.49 respectively). Notably, among the 16 patients who relapsed, 13 (81%) had a baseline TMTV baseline ≥ 155 mL. Upfront ABVD plus radiation therapy or upfront escBEACOPP without radiotherapy provide similar patient's outcome in high-risk stage IIB HL. TMTV is useful to stratify these patients at baseline.

The authors regret that the abstract that appears in the original article is incorrect. The correct abstract appears below. Introduction Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti- PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown.Methods We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine-learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. Results Forty patients from 14 centres were randomly assigned to training (n=25) and validation (n=15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0 – 33.5) months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N=27, 67.5%) or unacceptable toxicity (N=13, 32.5%). Most patients were in CR (N=35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine-learning algorithm identified that the most important variables to predict PFS were patients’ age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. Conclusion In this pilot, proof of concept study using a machine-learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients., SCOPUS: er.j, DecretOANoAutActif, info:eu-repo/semantics/published

Introduction: Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. Methods: We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. Results: Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0—time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients’ age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. Conclusion: In this pil, SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

We tested baseline PET/CT as a measure of total tumor burden in order to better identify high risk patients in early-stage Hodgkin's lymphoma (HL). Stage I-II HL patients enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after two cycles of doxorubicine, bleomycin, vinblastine, dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. IPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale. The prognostic value of TMTV was evaluated and compared to baseline characteristics, staging classifications and iPET2. A total of 258 patients were eligible, 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 PFS and 12 OS events. TMTV was prognosticator of PFS (p<0.0001) and OS (p=0.0001) with an 86% and 84% specificity respectively. The 5y-PFS and OS were 71% and 83% in the high TMTV (>147cm) group (n=46) vs. 92% and 98% in the low TMTV group (≤147cm). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared to the current staging systems proposed by EORTC/GELA, GHSG, or NCCN groups. TMTV and iPET2 were independently prognostic and combined identified four risk groups: low (TMTV≤147+DS1-3; 5y-PFS 95%), low-intermediate (TMTV>147+DS1-3; 5y-PFS 81.6%), high-intermediate (TMTV≤147+DS4-5; 5y-PFS 50%) and high (TMTV>147+DS4-5; 5y-PFS 25%). TMTV improves baseline risk stratification of early stage HL patients compared to current staging systems and the predictive value of early PET response as well.

Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti-PD-1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti-PD-1 therapy, assessed by PET-CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pretreated before anti-PD-1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti-PD1 therapy were progressive disease (PD) (n = 24) and partial response (PR) (n = 6). For the 24 PD patients, median anti-PD-1 related PFS was 7.5 months (95%CI, 5.7-11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti-PD-1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow-up of 12.1 months (7-14.7), the median PFS following the initiation of CT was 11 months (95% CI 6.3-not reached) and the median of overall survival was not reached. These observations in highly pretreated HL patients suggest that anti-PD-1 therapy might re-sensitize tumor cells to CT., SCOPUS: ar.j, info:eu-repo/semantics/published