Nivolumab for the treatment of relapsed and refractory classical Hodgkin lymphoma after ASCT and in ASCT-naïve patients

Abstract

About 70–80% of Hodgkin lymphoma patients can be cured with first-line chemotherapy [1]. In case of relapsed and refractory classical Hodgkin lymphoma (r/r cHL), second-line treatment and high-dose chemotherapy with autologous stem cells transplantation (ASCT) allow to achieve a sustained remission in half of the patients while the failure of ASCT defines poor prognosis [2,3]. Brentuximab vedotine (BV) leads to an objective response in 75% of patients relapsed after ASCT with a low rate of durable responses [4]. Results of Checkmate205 clinical trial demonstrated efficacy and safety of PD-1 inhibitor nivolumab in the treatment of r/r cHL patients after failure of ASCT and BV with 69% objective response and 92% 1-year overall survival (OS). At the moment, there is limited information regarding the efficiency and safety of nivolumab outside of clinical trials, with one report of real-life experience of nivolumab treatment (n1⁄4 82) showing similar response (64% ORR, 22% CR) at a median follow up of 7 months [6]. To date, there are no reports regarding the efficacy of nivolumab in ASCT-naïve r/r cHL patients. Another observation in the Chekmate205 study was the benefit of treatment beyond progression (TBP). TBP was associated with stable or reduced tumor burdens in 61% of patients and improved OS [5]. To overcome the limitations of current response criteria of progressive disease due to tumor flare or pseudo-progression, the LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) were proposed. Currently, there are no large cohorts reported with the implementation of LYRIC criteria in the treatment of r/r cHL patients. We report the results of single-center experience with nivolumab in 99 adult r/r cHL patients either failing after ASCT and/or BV and ASCT-naïve with response assessment based on LYRIC. This retrospective analysis included 99 adult patients with r/r cHL, treated in the First Pavlov Saint-Petersburg State Medical University. The study was approved by the institutional scientific review board; all of the participants provided written informed consent. Patients received nivolumab 3mg/kg intravenously every 2 weeks until unacceptable toxicity or treatment change due to disease progression. The [18F] fluorodeoxyglucose–positron emission tomography/computed tomography scanning (PET-CT) was performed before treatment initiation and further every 3 months. The PET-CT scanning results were prospectively assessed according to LYRIC criteria by a team of investigators which included treating physician, faculty staff member, and radiologist. In case of disease progression patients may have continued treatment beyond PET-CT assessed progression in case of stable performance status and evidence of clinical benefit. The primary endpoint was the OS; secondary endpoints included progression free survival (PFS), best overall response (BOR) and safety. The safety and tolerability were prospectively assessed and graded before each nivolumab cycle according to the NCI CTCAE v. 4.03. Data analysis was performed using SAS and SPSS software. The descriptive statistics methods were applied when appropriate. The impact of the previous therapy on response was tested with Chi-square and Kruskal-Wallis tests. OS and PFS were defined as the time from the start of nivolumab treatment to death or disease progression. Both OS and PFS were censored at the date of the last contact and were estimated using the Kaplan–Meier method. The difference in OS and PFS was tested with log-rank test. All patients (n1⁄4 99) were included in safety and efficacy analysis. Patients’ characteristics are presented in Table 1. At the time of the report, the median follow up was 21 months (7–26). The median age was 31 (19–61) years. At the start of the treatment, almost half of the