{'fraction_non_alphanumeric': 0.03907203907203907, 'fraction_numerical': 0.02543752543752544, 'mean_word_length': 5.11318407960199, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Can nivolumab alone cure patients with relapse or refractory Hodgkin lymphoma? A 5‐year analysis of the French early access program (EPA)

Checkpoint blockade with antiprogrammeddeath 1 (PD1) monotherapy has shown great efficacy in patients with relapsed/refractory Hodgkin lymphoma (R/R HL). 4 Patients who are unable to achieve a complete response (CR) usually experience limited progressionfree survival (PFS) in the absence of consolidation with allogenic haematopoietic stem cell transplantation (alloHSCT). Despite its curative potential, alloHSCT cannot be performed in all patients due to its particular toxicity profile after antiPD1 therapy. On the other hand, patients achieving a CR may experience durable remission without further therapy. These prolonged responses may persist even after antiPD1 discontinuation. It has been suggested that younger patients with an early and deep response have a higher probability of being relapsefree 1 year after antiPD1 discontinuation. However, in these studies, the median followup remained limited (median 1.5– 2.8 years) and data are lacking to assess whether some of these patients may be cured with antiPD1 therapy alone. Here, we report the 5year analysis of the Autorisation Temporaire d’Utilisationnivolumab (ATUnivo) study, a retrospective, nationwide study of patients aged ≥18 years with R/R HL who were treated with nivolumab in the French early access program (EAP). The study included patients with HL relapsing or refractory after three lines of chemotherapy (including brentuximabvedotin) and autoHSCT, or four lines of chemotherapy if the patient was not eligible for HSCT. All patients who had received at least one dose of nivolumab as part of the French EAP were eligible for the study. Nivolumab was administered at 3 mg/kg every 2 weeks until progression, death of any cause, unacceptable toxicity, consent withdrawal, or treating physician’s decision. Treatment efficacy was assessed using Ffluorodeoxyglucosepositron emission tomography/computed tomography. Patients were allowed to undergo subsequent alloHSCT according to primary physician’s decision. The protocol was approved by the Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé (CCTIRS; approval no. 16.861). The 3year analysis of the cohort has been previously published. We included 76 patients in the efficacy analysis. After a median followup of 5.7 years, the estimated 5year PFS and overall survival (OS) were 27% and 53% respectively. In all, 30 (39.5%) patients had a CR as best response, of whom 11 received a consolidation therapy: nine with an alloHSCT, one with an autoHSCT, and one with chemotherapy. As previously reported, patients in CR had a significantly better outcome than nonCR patients (Figure S1). To assess whether some patients might be cured with nivolumab alone as systemic treatment, we analysed the 19 patients who achieved a CR and did not receive a consolidation (concomitant radiotherapy was performed in five patients). Their characteristics are summarised in Table 1. These patients were young (median [range] age 39.4 [19– 77] years) and heavily pretreated with a median number of six prior systemic lines of treatment, including brentuximabvedotin (100%), autoHSCT (57.9%) and alloHSCT (36.8%). They received a median of 20 cycles of nivolumab. The median (range) time to CR was 2.1 (1– 5) months. All patients had discontinued nivolumab therapy at the time of analysis, mostly because of prolonged remission (52.6%) or adverse events (21%; two acute graftversushost disease, one laryngeal oppression and one cerebellar syndrome). Three (15.8%) patients discontinued because of disease recurrence and two (11.1%) because of nonhaematological malignancies. After a median followup of 5.6 years (4.0 years from nivolumab discontinuation), nine of 19 (47.4%) patients remained alive and disease free. The median PFS was 41.9 months and the median OS was not reached (Figure 1). The 5year estimated PFS was 42.3%. Nine patients have relapsed, of whom six received a salvage therapy: three received a second course of antiPD1, three received radiotherapy and/or chemotherapy. Half of the patients achieved a CR upon salvage therapy. Most relapses occurred within the first 2 years of treatment (seven patients). Two patients had late relapses, at 40 and 60 months after nivolumab initiation respectively. In total, two patients died: one due to metastatic colorectal cancer (6 months after nivolumab initiation) and one from coronavirus disease 2019 (COVID19.) There was no late adverse events reported. In the entire cohort (n = 76), the estimated 5year PFS was 27% after a median followup of 5.7 years, which is to the best of our knowledge, the longest followup ever reported in this setting. All patients who remain in remission had either Received: 1 March 2022 | Accepted: 31 March 2022