Abstract P108

Abscopal Effect of Radiotherapy and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma: Results of the International GHSG Phase II AERN Trial

Background: Failure of anti-PD1 treatment (aPD1) in patients (pts) with relapsed or refractory classical Hodgkin lymphoma (rrHL) is a clear unmet need. Whether the addition of local radiotherapy (RT) to aPD1 is effective and able to induce a systemic (“abscopal”) response (AR) in this setting is unknown.

Methods: The international GHSG phase II AERN trial (NCT03480334) enrolled rrHL pts with aPD1 failure as last line of therapy. They had to be enrolled latest 4 weeks after the last aPD1 dose without any intermittent therapy. In AERN, pts received 240mg nivolumab at 2-weekly intervals. Administration of 20Gy RT in 2Gy fractions to a single lesion started on day 6 after the first nivolumab dose on trial. The primary endpoint was AR, determined by the central review panel at first restaging after 6x nivolumab (RE-6). AR was defined as an objective response in ≥1 rrHL lesion ≥5 cm distant and outside the 10% isodose of the RT field. Nivolumab continued until progression, toxicity or a maximum of 18 months. Secondary endpoints included toxicity, objective response rate (ORR), progression-free (PFS) and overall survival (OS).

Results: A total of 25 pts (40% female) were enrolled with a median age of 37 years (range: 25-90) that had received a median of 4 (range 2-15) prior lines of therapy and predominantly presented with stage III/IV HL (88%) . Prior to enrollment, 72% had received autologous stem-cell transplantation, 72% brentuximab vedotin and 72% prior RT. All pts failed aPD1 (nivolumab: 60%, pembrolizumab: 40%) as last line of therapy and 96% experienced progressive disease immediately before enrollment. Of the 24 pts evaluable at RE-6, 11 (45.8%, 95%CI: 35.8-71.8%) achieved an AR, meeting the predefined efficacy endpoint. ORR was 33.4% (1 complete, 7 partial response) and 7 pts had stable disease (29.2%), for a disease control rate of 62.6%. Figure 1 summarizes changes in sum of product of diameters (SPD) and metabolic tumor volume (MTV) in evaluable pts. Ongoing analyses of longitudinal blood samples show significant associations of T- and NK-cell subsets with AR at RE-6 and additionally indicate a correlation between TARC dynamics and response.

Conclusions: The addition of local RT to aPD1 is feasible and effective in rrHL pts failing aPD1 treatment. It results in a systemic effect with AR, and overall complete or partial responses were observed. The final analysis of the AERN trial is currently ongoing and updated data will be presented at the meeti