Prognosis of patients with Hodgkin lymphoma and indeterminate response to PD-1 inhibitor therapy: considerations for application of LYRIC criteria in real clinical practice

PD-1 inhibitors have shown unconventional response patterns in classic Hodgkin lymphoma (cHL). These include the phenomenon of pseudoprogression, highlighting the need for specialized response criteria such as the LyRIC, which stringened definitions for disease progression with introduction of indeterminate response category. Despite their potential utility, these provisional criteria are currently underutilized and require further refinement through clinical practice data collection. In this retrospective study LyRIC criteria were systematically used for response assessments in 180 patients with refractory cHL treated with nivolumab. Median follow-up was 60 months. Indeterminate response (IR) was a frequent phenomenon in study population: at 3 months of therapy 63 (35%) patients had an indeterminate response (IR1 7%, IR2 23%, IR3 6%). Among them 18 (29%) achieved an objective response with continued monotherapy. There were no differences in OS or TTNT depending on the type of IR. IR was the best achieved response in 45 (25%) patients. Patients with IR had favorable prognosis with no difference in OS, PFS and TTNT comparing to patients with PR when subsequent therapy was initiated due to disease progression. Patients with IR may achieve prolonged disease control or a deeper response upon continuing treatment. These findings support the broader implementation and adjustment of LyRIC criteria in clinical practice to enhance decision-making in cHL patients treated with immunotherapy.