Abstract P004

Low-dose nivolumab combined with AVD chemotherapy (Nivo40-AVD) for advanced classic Hodgkin lymphoma: interim results

Background: Nivolumab plus AVD (N-AVD) is currently approved for newly diagnosed advanced-stage classical Hodgkin lymphoma (cHL). However, substantially lower nivolumab doses (0.1–0.33 mg/kg) have demonstrated clinical activity in relapsed/refractory settings. We evaluated the efficacy and safety of a low-dose nivolumab regimen (Nivo40-AVD) in untreated advanced cHL.

Methods: This is an interim analysis of an investigator-initiated phase II trial (NCT06984146). Eligible patients were ≥18 years with stage IIB disease with bulky mediastinal mass and/or extranodal involvement, or stage III–IV cHL, with adequate cardiac function and no history of autoimmune disease. Exclusion criteria were uncontrolled infection, decompensated organ failure unrelated to lymphoma, pregnancy, and inability to consent. Treatment consisted of six cycles of Nivo40-AVD (nivolumab 40 mg; doxorubicin 25 mg/m2; vinblastine 6 mg/m2; dacarbazine 375 mg/m2 on days 1 and 15). PET/CT was performed after cycle 2 and at the end of treatment. Consolidative radiotherapy was permitted for partial response. The primary endpoint was 2-year progression-free survival (PFS); secondary endpoints included overall response rate (ORR), complete response (CR), overall survival (OS), and adverse events rate.

Results: At data cutoff, 35/54 patients were enrolled; 20 (57%) completed therapy and were evaluable. Median age was 36 years (range 19–73). Most patients had stage IV disease (55%), B-symptoms (80%), extranodal involvement (70%), and nodular sclerosis subtype (95%); 75% were female. EBV positivity was observed in 15%. Median nivolumab dose was 0.56 mg/kg (range 0.35–0.74). ORR was 100%, with CR in 90% of patients. At a median follow-up of 10 months, PFS was 100%. Grade 3–4 adverse events included neutropenia (65%) and transaminitis (10%).

Conclusions: Low-dose nivolumab combined with AVD is feasible and demonstrates promising efficacy as frontline therapy for advanced cHL. Follow-up is ongoing. Updated results will be presented at the meeting.