Abstract P020

Efficacy and Safety of the combination of Programmed Death -1 inhibitors (PD-1i) with chemotherapy for the treatment of classical Hodgkin’s Lymphoma (cHL). A single center experience

Background: Although efficacy and toxicity of the continuous treatment of PD-1i is well documented, less is known about their combination with chemotherapy.

Aim: Our aim is to provide real-word data on this topic.

Methods: We report outcomes and toxicities of 11 subjects treated with Nivolumab+AVD as 1L for advanced stage cHL (AS-cHL) and 6 other salvaged with Pembrolizumab+GVD for primary refractory disease.

Results: Between 2023-2026, 2 men and 9 women, median age 61y (51-70), were newly diagnosed with AS-cHL. The subtypes were nodular sclerosis (NS) in 5, mixed cellularity (MC) in 3, lymphocyte-rich (LRcHL) in 3 cases. Ann Arbor stage was III in 8, IV in 3 patients. Seven patients concluded 6 cycles, 3 interrupted due to toxicity and 1 is on treatment. iPET was performed in 9: DS2 n=5, DS3 n=2, DS1 n=1, DS4 n=1. EoT PET was performed in 8 patients: DS2 n=4, DS3 n=3, DS5 n=1. All had GCSF prophylaxis. Treatment-related toxicities were observed in 7 patients: Acute heart failure, rash, hypothyroidism, thrombocytopenia with hemorrhagic manifestations, anemia, stomatitis, cataract. Febrile neutropenia requiring hospitalization was manifested in 4 (36%) and hepatotoxicity >= grade 3 in 4 (36%) patients. Among them a woman died due to liver failure, while delayed hepatic fibrosis occurring 6 months after treatment completion was observed in another case. With a mfollow up of 27.7 months (0.9-34), all patients but 1 are alive. The mPFS is 18.93 months (5.17-31.8) with 3 (27%) patients relapsing after achieving CR and 1 dying in CR. Median OS was not reached. Between 2024 -2026, 3 men and 3 women, median age 51y. (33-69) with primary refractory cHL-NS, after treatment with BrECADD (n=2) and ABVD (n=4) were salvaged with PembroGVD. The Ann Arbor stage was II (n=1), III (n=3) and IV (n=2). One patient is on treatment and 5 completed it: Four achieved CMR and 3 underwent ASCT. A 4th patient manifested acute heart and renal failure, becoming ineligible for ASCT. The 5th subject showed resistant disease and died thereafter. One patient was intubated due to severe pulmonary toxicity and another 1 for aseptic meningitis, 2 developed hypothyroidism, 1 hepatotoxicity. With a mfollow up of 17.8 months (0.6-20.8), all patients but 1 are alive. MedianOS was not reached. Among patients who achieved CR nobody relapsed.

Conclusions: Combining PD-1i with chemotherapy is efficacious, but it demonstrates significant toxicity, more than it is described in the pivotal trials.