Nivolumab for classical Hodgkin lymphoma after autologous stem-cell transplantation and brentuximab vedotin failure: a prospective phase 2 multi-cohort study
By A. Younes, A. Santoro, M. Shipp, P. Zinzani, J. Timmerman, S. Ansell, P. Armand, M. Fanale, V. Ratanatharathorn, J. Kuruvilla and 11 more. The Lancet Oncology, 2016
762 citations recorded by the source corpus.
Background Malignant cells of classical Hodgkin lymphoma (cHL) are characterised by genetic alterations at the 9p24·1 locus. This leads to overexpression of the programmed death 1 (PD-1) ligands and enables tumour cells to evade immune surveillance. A phase 1b study showed that nivolumab, a PD-1-blocking antibody, produced a high response rate in patients with relapsed and refractory cHL, with an acceptable safety profile. This phase 2 study assessed the clinical benefit of nivolumab monotherapy in patients with cHL after autologous stem-cell transplantation and brentuximab vedotin failure. Methods This ongoing phase 2 study (NCT02181738) assessed the efficacy and safety of nivolumab, administered intravenously over 60 minutes at 3 mg/kg every 2 weeks, in adult patients with cHL who had failed both autologous stem-cell transplantation and brentuximab vedotin. The primary endpoint was objective response rate by independent radiologic review committee (IRRC) assessment. Secondary and other endpoints included duration of response, safety, and assessment of PD-L1 and PD-L2 loci and PD-L1 and PD-L2 protein expression. Findings Among 80 treated patients, the median number of prior therapies was four (range 3–15). With a mean (SD) follow-up of 8·6 months (2·02), objective response rate per IRRC was 66·3% (53/80). The most common drug-related adverse events (≥15%) included fatigue, infusion-related reaction, and rash. The most common drug-related grade 3–4 adverse events were neutropenia and increased lipase levels (both n=4). The most common serious adverse event (any grade) was pyrexia (n=3). Interpretation Nivolumab demonstrated a high response rate and an acceptable safety profile in patients with cHL who progressed following autologous stem-cell transplantation and brentuximab vedotin. Nivolumab may therefore provide a novel treatment option for a patient population with a high unmet need. Ongoing follow-up will help to assess the durability of response. Funding Bristol-Myers Squibb.
Subfields: Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/8f7e0764d7d50dc58a48cbf9dd89c9cb4a63d968
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Citations in the corpus
- Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations (2018, methodology): “The CheckMate 205 trial was a phase II study enrolling 80 patients with cHL who had relapsed after ASCT or BV to receive nivolumab 3 mg/kg every 2 weeks [46].”
- Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial (2018, neutral): “Median age, years (IQR) 33 (26-45) 37 (28-48) 32 (25-47) 34 (26-46) $ 60 5 (8) 7 (9) 3 (3) 15 (6) Male 34 (54) 51 (64) 56 (56) 141 (58) ECOG PS 0 39 (62) 42 (53) 50 (50) 131 (54) 1 24 (38) 38 (48) 50 (50) 112 (46) Disease stage at study entry I 1 (2) 1 (1) 2 (2) 4 (2) II 20 (32) 11 (14) 20 (20) 51 (”
- Acquired Resistance to Immune Checkpoint Inhibitors (2020, background): “We have attempted to infer the rates of acquired resistance based upon available duration of response data among different tumor types (Antonia et al., 2019; Armand et al., 2018; Balar et al., 2018; Burtness et al., 2019; Chen et al., 2019a; Cohen et al., 2019; Fehrenbacher et al., 2018; Fradet et a”