Experience with prolgolimab in the treatment of patients with relapsed and refractory classical Hodgkin lymphoma

Abstract Background: Modern treatment regimens for classical Hodgkin lymphoma (cHL) enable the cure of the majority of patients; however, relapse or refractory disease (r/r cHL) occurs in approximately 20–25% of cases. The standard second-line treatment for young patients includes high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT). The introduction of PD-1 inhibitors both during remission induction prior to auto-HSCT and as consolidation therapy post-transplant has significantly improved outcomes in this patient population. Prolgolimab is a human monoclonal antibody that specifically binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2 ligands on tumor cells. It is hypothesized that adding prolgolimab to a standard salvage chemotherapy regimen may increase the rate of complete remission, which is a key factor in the success of subsequent auto-HSCT. Objective: To evaluate the efficacy and safety of prolgolimab both as monotherapy and in combination with DHAP chemotherapy (dexamethasone, cytarabine, cisplatin), as well as to assess the feasibility of peripheral blood stem cell (PBSC) collection followed by auto-HSCT in patients with r/r cHL. Materials and Methods: This study analyzed data from 20 patients with r/r cHL treated at the N.N. Blokhin National Medical Research Center of Oncology. The treatment protocol included two doses of prolgolimab monotherapy at 1 mg/kg administered every 14 days, followed by two cycles of prolgolimab in combination with DHAP. In cases of partial or complete remission based on PET/CT, PBSC apheresis was performed, followed by auto-HSCT. After transplantation, patients underwent PET/CT evaluation and received consolidation therapy with prolgolimab monotherapy (a total of 8 doses). Results: Twenty patients (7 males and 13 females) were diagnosed with r/r cHL following first-line therapy with ABVD or BEACOPP regimens. Two patients experienced isolated elevations in hepatic transaminases (ALT, AST) up to 6 times the upper limit of normal during the combination therapy phase, but such changes were not observed during monotherapy. One patient developed immune-mediated hypothyroidism and was started on hormone replacement therapy. One patient died of pulmonary embolism (PE) during disease progression. Complete metabolic response on PET/CT (Deauville score 2–3) was observed in 11 patients, and partial response (Deauville score 4) in 3 patients. Disease progression was noted in 6 patients, who were subsequently switched to bendamustine-based chemotherapy regimens. PBSC collection was successfully performed in 15 patients after chemomobilization with etoposide (375 mg/m²/day on days 1–2). Adequate PBSC yields were achieved after one apheresis session in 9 patients, two sessions in 5 patients, and three sessions in 1 patient. The median CD34+ cell count collected was 5.6 × 10^6/kg (range: 2.23–19.65 × 10^6/kg), sufficient for auto-HSCT. Fourteen patients underwent auto-HSCT. Nine patients completed consolidation therapy with prolgolimab monotherapy after transplantation. All patients who completed the planned treatment protocol are alive with no evidence of disease progression. Conclusion: The combination of prolgolimab with DHAP chemotherapy is highly effective and safe, with no negative impact on PBSC collection. Achieving tumor response prior to auto-HSCT and the use of prolgolimab as consolidation therapy can lead to durable remissions without additional toxicity in patients with r/r cHL.