Adjusted Indirect Comparison Between Epcoritamab‐R 2 and Tafasitamab‐R 2 in Relapse/Refractory Follicular Lymphoma

ABSTRACT Treatment of relapsed refractory follicular lymphoma (R/R FL) still remains challenging. Several strategies have been used against R/R FL. Recently, two chemotherapy‐free regimens have gained space, epcoritamab‐lenalidomide‐rituximab (Epco‐R 2 ) and tafasitamab‐lenalidomide‐rituximab (Tafa‐R 2 ). Herein, we performed an indirect trial comparison (ITC) between the two regimens using the Bucher method as they both have the common comparator arm R 2 . The ITC between the two study arms showed an overall response rate (ORR; p = 0.020), and complete remission rates (CR; p < 0.0001), in favor of Epco‐R 2 . Analysis regarding time to next treatment (TTNT) interval also favored Epco‐R 2 ( p = 0.0011). The ITC in the progression free survival (PFS) context showed the anchored comparison favored Epco‐R 2 over Tafa‐R 2 [HR 0.51 (95% CI 0.31–0.86)], p = 0.011, a finding more pronounced in patients with progression of disease within 24 months (POD24) negativity. Regarding the safety profile, Epco‐R 2 was associated with more hematological toxicity and infections, whereas, Tafa‐R 2 was associated with more COVID‐19 infections probably reflecting the pandemic era enrollment timing. In conclusion, Epco‐R 2 is more effective in terms of treatment outcomes, but comes with greater toxicity. Tafa‐R 2 seems more suitable for patients with limited bone marrow reserves, patients who wish to avoid hospitalization, patients at a higher risk for cytokine release syndrome, and patients with high‐risk infection vulnerability. Finally, this is not a direct comparison of two therapeutic regimens and the results should be cautiously interpreted. Treatment choice should be decided on a case‐by‐case scenario based on several different variables.