The RESONATE trial compared ibrutinib, a Bruton’s tyrosine kinase inhibitor, with ofatumumab, an anti-CD20 antibody, in patients with previously treated chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL). The study enrolled 391 patients who had relapsed or refractory disease and were ineligible for purine analogue therapy. Patients were randomly assigned to receive either daily ibrutinib or ofatumumab for up to 24 weeks. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and overall response rate (ORR) as secondary endpoints. At a median follow-up of 9.4 months, ibrutinib significantly improved PFS compared to ofatumumab, with the median PFS not reached in the ibrutinib group (88% at 6 months) versus 8.1 months in the ofatumumab group (hazard ratio 0.22, P<0.001). Ibrutinib also significantly improved OS (hazard ratio 0.43, P=0.005), with 90% OS at 12 months versus 81% in the ofatumumab group. The ORR was significantly higher in the ibrutinib group (42.6% vs. 4.1%, P<0.001). Additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. These benefits were observed regardless of prior resistance to purine analogues or chromosome 17p13.1 deletion. Ibrutinib was generally well tolerated, with common non-hematologic adverse events including diarrhea, fatigue, and pyrexia. Ofatumumab was associated with fatigue, infusion-related reactions, and cough. Serious adverse events were less frequent in the ibrutinib group. The study showed that ibrutinib significantly improved PFS, OS, and ORR in patients with previously treated CLL or SLL, regardless of baseline characteristics. The results were consistent across subgroups, including those with high-risk genetic features. Ibrutinib was associated with a lower risk of progression or death compared to ofatumumab. The study was funded by Pharmacyclics and Janssen, and the results support the use of ibrutinib as a first-line treatment for patients with relapsed or refractory CLL or SLL.The RESONATE trial compared ibrutinib, a Bruton’s tyrosine kinase inhibitor, with ofatumumab, an anti-CD20 antibody, in patients with previously treated chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL). The study enrolled 391 patients who had relapsed or refractory disease and were ineligible for purine analogue therapy. Patients were randomly assigned to receive either daily ibrutinib or ofatumumab for up to 24 weeks. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and overall response rate (ORR) as secondary endpoints. At a median follow-up of 9.4 months, ibrutinib significantly improved PFS compared to ofatumumab, with the median PFS not reached in the ibrutinib group (88% at 6 months) versus 8.1 months in the ofatumumab group (hazard ratio 0.22, P<0.001). Ibrutinib also significantly improved OS (hazard ratio 0.43, P=0.005), with 90% OS at 12 months versus 81% in the ofatumumab group. The ORR was significantly higher in the ibrutinib group (42.6% vs. 4.1%, P<0.001). Additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. These benefits were observed regardless of prior resistance to purine analogues or chromosome 17p13.1 deletion. Ibrutinib was generally well tolerated, with common non-hematologic adverse events including diarrhea, fatigue, and pyrexia. Ofatumumab was associated with fatigue, infusion-related reactions, and cough. Serious adverse events were less frequent in the ibrutinib group. The study showed that ibrutinib significantly improved PFS, OS, and ORR in patients with previously treated CLL or SLL, regardless of baseline characteristics. The results were consistent across subgroups, including those with high-risk genetic features. Ibrutinib was associated with a lower risk of progression or death compared to ofatumumab. The study was funded by Pharmacyclics and Janssen, and the results support the use of ibrutinib as a first-line treatment for patients with relapsed or refractory CLL or SLL.