Clinical outcomes of the chemo‐free approach in relapsed/refractory follicular lymphoma: A network meta‐analysis

Summary Relapsed/refractory follicular lymphoma (R/R FL) remains a clinically challenging condition, with progressively declining benefit across consecutive lines of therapy. While anti‐Cluster of Differentiation 20 (CD20) antibodies remain the therapeutic backbone, the optimal targeted or immune‐based partner remains undefined. A systematic review and network meta‐analysis (NMA) of 5 phase III and 1 phase II trials (2500 patients) evaluated seven anti‐CD20‐based combination strategies. Primary end‐points were overall survival (OS) and progression‐free survival (PFS); secondary end‐points included objective response rate (ORR) and grade ≥3 adverse events. Treatments were ranked using surface under the cumulative ranking (SUCRA) values. Immune‐activating strategies ranked highest across efficacy end‐points. Epcoritamab plus rituximab (R 2 ) achieved the top SUCRA rankings for OS, PFS and ORR, while tafasitamab plus R 2 consistently ranked second, with a better safety profile. R 2 alone showed intermediate efficacy and good tolerability, whereas zanubrutinib plus anti‐CD20 demonstrated modest efficacy with lower toxicity. Bortezomib and copanlisib‐based combinations ranked lowest for efficacy, with phosphoinositide 3‐kinase (PI3K) inhibitor–based regimens showing the least favourable benefit–risk profile. Anti‐CD20 monotherapy was the safest but least effective option. This NMA indicates that immune‐centric, anti‐CD20‐anchored combinations represent the most effective chemotherapy‐free strategies for R/R FL. Combinations incorporating anti‐CD19 or CD20/CD3 bispecific antibodies appear to offer deeper disease control, particularly in high‐risk and rituximab‐refractory disease.