Stephen M. Ansell1,*, Philippe Armand2, John M. Timmerman3, Margaret A. Shipp2, Ulrich Jäger4, Wolfgang Willenbacher5, Rao Saleem6, Julia He6, Mariana Sacchi6, Anne Sumbul6, Alexander M. Lesokhin7
1Mayo Clinic, Rochester, MN, USA,2Dana-Faber Cancer Institute, Harvard Medical School, Boston, MA, USA,3Jonsson Comprehensive Cancer Centre, UCLA, Los Angeles, CA, USA,4Medical University of Vienna, Vienna, Austria,5Innsbruck University Hospital & OncoTyrol – Center of Personalized Cancer Medicine, Innsbruck, Austria,6Bristol-Myers Squibb, Princeton, NJ, USA,7Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA
Background: Nivolumab (nivo), a fully human IgG4 anti-PD-1 monoclonal antibody immune checkpoint inhibitor, demonstrated acceptable safety and frequent and durable responses in phase 1 (NCT01592370) and phase 2 (NCT02181738) trials including patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) [1–3]. However, the optimal duration of treatment is still unknown and may depend on re-treatment outcomes in patients who progress off therapy. A subgroup of patients from these studies who stopped nivo treatment in remission and later progressed were eligible for re-treatment.
Aim: To assess the safety and efficacy of nivo re-treatment in patients with progressive disease (PD) after stopping therapy in remission.
Methods: In the phase 1 study, patients with R/R cHL were initially treated with nivo (3 mg/kg every 2 weeks) until PD, complete remission (CR), or unacceptable toxicity, for up to 2 years. Patients with ongoing disease control (CR, partial remission [PR], or stable disease) were eligible for re-treatment upon confirmed PD in ≤1 year from last nivo dose. In the phase 2 study, patients in Cohort C with R/R cHL who received prior brentuximab vedotin before and/or after autologous hematopoietic cell transplantation and achieved CR for ≥1 year were eligible for re-treatment upon confirmed PD in ≤2 years from last nivo dose. Toxicity and response to re-treatment were assessed.
Results: At data cut-off (May 2017), 5 patients from the phase 1 study were re-treated with nivo (age 26–53 years; 4 female; ECOG performance status 0–1). All patients achieved CR (n = 1) or PR (n = 4) after 8–18 weeks of re-treatment (Table). One patient remained in PR and was still on re-treatment at data cut-off. In the initial treatment period, all patients had treatment-related adverse events (TRAEs; 1 grade 3 lymphopenia; all others grade 1–2). With re-treatment, 1 patient had grade 2 neutropenia after 18 doses; all other TRAEs were grade 1. In the phase 2 study, 2 patients entered re-treatment. Safety and response analyses from these patients based on a May 2018 database lock will be presented.
Conclusions: Re-treatment with nivo can lead to high response rates with tolerable safety. These data provide further evidence of re-treatment benefit in patients with disease progression after initial response.
References: 1. Ansell SM et al. N Engl J Med 2015;372:311–9; 2. Ansell SM et al. ASH 2015 [Oral 583]; 3. Armand P et al. J Clin Oncol 2018;36:1428-39