Patterns of Progression After Immune Checkpoint Inhibitors for Hodgkin Lymphoma: Implications for Radiation Therapy.

Immune checkpoint inhibitors (ICI) have demonstrated remarkable response rates in relapsed or refractory Hodgkin lymphoma (HL). Still, most patients eventually progress. Patterns of progression after ICI are not well described, and are essential to define the role of local therapies in combination with ICI. We identified patients who received ICI for HL between 2013-2022. FDG-PET before initiating ICI and at progression on/after ICI were reviewed, and areas of active HL were recorded. An exploratory analysis of "treatable progression" included patients with <5 sites of disease on pre-ICI FDG-PET and progression only at pre-ICI sites. Ninety patients were identified, 69 had complete records, and of these 32 (52%) had relapsed at ICI initiation, 17 (25%) were refractory, and 16 (23%) received ICI as first-line therapy. Forty-five of 69 patients had <5 sites of disease ("limited") on pre-ICI FDG-PET. Patients with >5 sites of disease had a higher risk of progression, and every site of disease >5 sites conferred an additional 1.2x higher chance of progression. At median follow-up of four years, 41/69 patients had progressed on/after ICI (cumulative incidence 66.4%), and of these, 22/41 patients progressed only at pre-ICI sites (cumulative incidence 39.4%). In an exploratory analysis, the cumulative incidence of a treatable progression among 45 patients with "limited" disease was 34%. Cumulative incidence of any progression among this cohort was 58.9%. More than one-third of patients with "limited" disease before ICI experienced progression only at pre-ICI sites of disease. These patients could be candidates for radiation during or after ICI.