ABSTRACT Therapy for relapsed or refractory (R/R) aggressive B‐cell non‐Hodgkin lymphoma (aB‐NHL) post autologous stem cell transplantation (ASCT) or in elderly patients can be challenging. In this single‐center, single‐arm, phase II clinical study, we investigated the efficacy of ibrutinib (560 mg once daily) in combination with bendamustine and rituximab (IBR) given for six 28‐day cycles in their standard dose, to patients with R/R aB‐NHL who were either transplant ineligible in first or second relapse or post‐ASCT for second relapse. The primary endpoint was overall response rate (ORR). Fifty‐six patients (54% male, median age 69.7 years) were included. ORR was 49.1% among 55 patients treated with ≥ 1 cycle of IBR and 69.4% among 36 patients treated with ≥ 3 cycles. Patients with relapsed disease had significantly higher ORR compared to those with refractory disease (72.3% vs. 37.8%, p = 0.024). Median overall survival (OS) was 11.6 months (95% CI, 7.1–22.3) and median progression‐free survival was 5.3 months (95% CI, 2.5–7.4). Patients with complete and partial responses had significantly longer median OS compared to those with stable and progressive disease (28.1 vs. 5.2 months, p &lt; 0.0001). Adverse events included thrombocytopenia (19.6%), anemia (16.1%), neutropenia (7.1%), fatigue (35.7%), diarrhea (28.6%) and nausea (28.6%). At the first efficacy evaluation 8 patients were referred to transplantation, and 3 more were referred during follow‐up. These data indicate that the IBR regimen is a safe and effective treatment option that can also be used for bridging to transplantation in patients with R/R aB‐NHL. Trial Registration: ClinicalTrials.gov : NCT02747732

Ibrutinib With Bendamustine and Rituximab for Treatment of Patients With Relapsed/Refractory Aggressive B‐Cell Lymphoma