Ann Oncol 2017 Oct 1;28(10):2496-2502

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

Beköz H1, Karadurmus N2, Paydas S3, Türker A4, Toptas T5, Firatli Tuglular T5, Sönmez M6, Gülbas Z7, Tekgündüz E8, Kaya AH8, Özbalak M9, Tastemir N10, Kaynar L11, Yildirim R12, Karadogan I13, Arat M14, Pepedil Tanrikulu F15, Özkocaman V16, Abali H17, Turgut M18, Kurt Yüksel M19, Özcan M19, Dogu MH20, Kabukçu Hacioglu S21, Barista I4, Demirkaya M22, Köseoglu FD23, Toprak SK19, Yilmaz M24, Demirkürek HC25, Demirkol O26, Ferhanoglu B27.
Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile.
l="Background" NlmCategory="UNASSIGNED">Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile.

Patients and methods:

We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively.

Results:

Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related.

Conclusions:

Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.