Abscopal response observed in HL patients who failed on anti-PD treatment

Treatment with nivolumab and radiotherapy at a single lesion is well tolerated and leads to an abscopal response in the majority of the relapsed/refractory HL cases.

The response was observed in patients with with relapsed or refractory HL with anti-PD treatment failure

Anti-PD1 blockade has proven to be highly effective and is approved for the treatment of relapsed/refractory Hodgkin lymphoma. In addition, the progression-free survival (PFS) and overall survival (OS) outcomes are superior in patients achieving a complete response to anti-PD1 therapy1. However, most patients eventually develop progression of disease, constituting an unmet need due to a lack of approved novel treatment options. Local radiotherapy is postulated to induce systemic anti-tumour immunity leading to a tumour response outside the irradiated area. This so-called abscopal effect may be augmented by anti-PD1 therapy2.

The ongoing AERN (Abscopal Effect of Radiotherapy and Nivolumab in Relapsed or Refractory Hodgkin Lymphoma) trial (NCT03480334) is a phase-2, proof-of-concept study to prospectively evaluate the efficacy and safety of nivolumab and radiotherapy in patients with relapsed/refractory Hodgkin lymphoma who failed on anti-PD1 treatment. Dr Paul Bröckelmann (University Hospital of Cologne, Germany) presented the results of the first pre-planned interim analysis3.

In many cases, a response was observed in lesions far from the radiated area

The study enrolled 29 patients (n=9 in stage I, n=20 in stage II) who showed progressive disease while on anti-PD1 treatment or stable disease for more than 6 months as best response while on active treatment. The last dose of anti-PD1 was within 4 weeks prior to enrolment. Patients had ≥2 distinct FDG-avid lesions with at least 5 cm distance between them and one lesion considered to be eligible for radiotherapy with 20 Gy. Radiotherapy was administered after the first dose of nivolumab. The primary endpoint is abscopal response rate at the first interim restaging after 6 infusions. 

In the participants enrolled in stage I, the overall response rate at first interim restaging was 56% (all partial responses), and abscopal response rate was present in 56% (n=5) of patients. In many cases, lesions far away from the radiated area showed a response. Even a patient who was classified as progressive due to a new lesion had a substantial reduction of tumour burden in the non-radiated lesions. PFS at 1 year is 42.3%. 

The treatment was well tolerated: most adverse events were grade 1, mostly skin toxicity due to radiotherapy. 
Based on these preliminary results, Dr Bröckelmann concluded that radiation combined with anti-PD1 treatment is feasible and safe in patients with relapsed/refractory Hodgkin lymphoma who failed on anti-PD1 treatment. In addition, the results show encouraging early signals of efficacy, in particular an abscopal response rate of 56%. “This warrants further enrolment of patients in the trial.”

References: 
1. Ansell SM, et al. Abstract 074. International Conference on Malignant Lymphoma 2021, 18–22 June.
2. Ngwa W, et al. Nat Rev Cancer. 2018;18:313–322.
3. Bröckelmann P, et al. Abscopal effect of radiotherapy and nivolumab in relapsed or refractory Hodgkin lymphoma: pre-planned interim analysis of the international GHSH phase II AERN trial. Abstract S203. EHA2022 Hybrid Congress, 09–12 June.