Summary The activity and safety of two‐weekly dose‐adjusted (DA)‐EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)‐like chemotherapy with high‐dose dexamethasone plus rituximab (DA‐EDOCH14‐R) was explored in 20 patients with previously untreated poor prognosis diffuse large B‐cell lymphoma (DLBCL). The main outcomes were compared with those of 27 poor‐prognosis patients enrolled into a previous trial of 3‐weekly DA‐EPOCH‐R. Toxicity was manageable and there were no therapy‐related deaths. Three‐year progression‐free survival (PFS) was superior in the DA‐EDOCH14‐R group (95% vs. 74%, P = 0·08). Importantly, this improvement in PFS with the two‐weekly DA‐EDOCH14‐R was particularly notable in patients with an age‐adjusted International Prognostic Index of 3 (100% vs. 30%, P < 0·001).

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