Abstract P104

Pembrolizumab In Relapsed/Refractory Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Case Report

Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy, accounting for 5-6% of Hodgkin lymphomas, usually with very favorable outcomes. However, 20-30% of patients will relapse, with a 10-year risk of transformation into an aggressive large B-cell Lymphoma of 4-10%. The management of relapsed/refractory (R/R) NLPH remains challenging. While PD-1 blockade has established activity in classical Hodgkin lymphoma, data in NLPHL are scarce.

Case Report: A 24-year-old male presented in 2018 with stage IIA NLPHL (unknown histological variant at diagnosis), located in the inguinal region. He was first treated with 4 cycles of ABVD and involved-field radiotherapy but relapsed 2 years later, with retroperitoneal disease and B symptoms. A new biopsy confirmed NLPHL and he received rituximab monotherapy (4 infusions), achieving a partial response. A year later he complained of lumbar pain and stage IV disease was demonstrated, with multiple extranodal sites (pleural, peritoneal and bone marrow). Third line with ESHAP was started, with the intention to consolidate with high dose chemotherapy and autologous stem cell transplantation (SCT), but no response was obtained. At this time a new biopsy excluded transformation and showed a type D histological variant. Stage IV disease was present. The patient started a fourth line with rituximab-bendamustine, again progressing under treatment and requiring dorsal radiotherapy for pain control. A new biopsy confirmed persistence of NLPHL with PD1 expression in tumor microenvironment T-Cells. At this time a sixth line treatment was proposed with pembrolizumab monotherapy. After 6 cycles complete metabolic response (CMR) was achieved, with resolution of extensive nodal, pleural, pulmonary, paravertebral and bone disease. Patient then underwent consolidation with allogeneic SCT with a matched unrelated donor and reduced intensity conditioning in March 2026. Complete metabolic response is ongoing.

Conclusion: This case illustrates the potential use of PD-1 blockade as an effective salvage and bridging strategy to allogeneic SCT in the rare instance of heavily pre-treated NLPHL. Durable CMR was achieved in this patient, previously refractory to five chemotherapy regimens. This data support further investigation of checkpoint inhibition at earlier lines in this uncommon lymphoma subtype.