Optimizing Resources: Low-Dose Nivolumab Combinations in the Management of Relapsed/Refractory Hodgkin Lymphoma, a Real-World Experience

Introduction:Up to one-third of patients with Hodgkin's lymphoma (HL) are not responsive to first-line therapy or eventually relapse. For these patients, second-line chemotherapy followed by autologous stem cell transplantation (ASCT) represents the standard of care, with better results for those that respond to salvage chemotherapy, usually achieving higher survival after ASCT, however, this strategy is far from perfection. In recent years, immunotherapy has brought with it novel agents, including monoclonal antibodies and antibody-drug conjugates, that have revolutionized the therapeutic landscape for relapsed or refractory Hodgkin's lymphoma (r/r HL). Anti-programmed death protein 1 antibodies (e.g. nivolumab, pembrolizumab) and anti-CD30 drug, brentuximab vedotin (BV), are two popular examples from the above-mentioned drug classes that have proven both acceptable results and exorbitant prices, unsustainable for patients and health systems from Low- and Middle-income countries. Although pivotal trials indicate that the ideal doses for nivolumab use are 3 mg/kg or 240 mg fixed dose, emerging evidence suggests that full receptor occupation can be achieved with lower nivolumab doses and it has been successfully employed for the treatment of hematologic malignancies in doses as low as 40 mg fixed dose. Objective: In this study, we present our real-world experience exploring different combinations commonly used with standard-dose nivolumab, now with lower doses and costs. Methods:We retrospectively analyzed patients that fulfilled the following criteria: ≥16 years old, diagnosis of relapsed or refractory HL, treated with low-dose nivolumab in any flat low-dose (40, 100, or 140 mg) in any combination with other agents. We retrieved data from their electronic medical record and follow-up imaging studies (CT-Scan or PET-CT). We analyzed the response to therapy using the Deauville score. OS and PFS were analyzed with Kaplan-Meier curves. Survival analyses by treatment regimen and nivolumab subgroups were compared for statistically significant differences by means of the log-rank test. A value of p < 0.05 was considered statistically significant for all tests. Results: A total of 23 patients were included in our study. 57% (n = 13) were women. The median age was 27 years (20-30). Complete baseline characteristics are displayed in Table 1. Most of the patients (73%, n = 17) achieved an objective response, 43% (n = 10) a complete response (CR), and 30% (n = 7) a pa