A phase 1b-2 trial evaluated ibrutinib, a first-in-class oral BTK inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. The study enrolled 85 patients, most with high-risk disease, who received 420 mg or 840 mg of ibrutinib daily. The overall response rate was 71% in both groups, with 20% and 15% of patients showing partial responses with lymphocytosis. The response was independent of clinical and genomic risk factors. At 26 months, the estimated progression-free survival rate was 75% and overall survival was 83%. Ibrutinib was well tolerated, with mostly grade 1 or 2 adverse events, including diarrhea, fatigue, and upper respiratory tract infections. Serious adverse events were rare, and the drug showed no significant increase in infection rates compared to traditional therapies. Ibrutinib demonstrated durable remissions, with 71% response rate and 75% progression-free survival at 26 months. The drug effectively inhibited BTK, leading to reduced lymphocyte counts and improved cytopenias. Ibrutinib was effective regardless of the dose and showed no significant difference in response based on mutation status of the immunoglobulin variable-region heavy-chain gene. The study supports the use of ibrutinib for relapsed CLL, with potential for monotherapy. Ongoing trials are evaluating its efficacy in combination with other agents.A phase 1b-2 trial evaluated ibrutinib, a first-in-class oral BTK inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. The study enrolled 85 patients, most with high-risk disease, who received 420 mg or 840 mg of ibrutinib daily. The overall response rate was 71% in both groups, with 20% and 15% of patients showing partial responses with lymphocytosis. The response was independent of clinical and genomic risk factors. At 26 months, the estimated progression-free survival rate was 75% and overall survival was 83%. Ibrutinib was well tolerated, with mostly grade 1 or 2 adverse events, including diarrhea, fatigue, and upper respiratory tract infections. Serious adverse events were rare, and the drug showed no significant increase in infection rates compared to traditional therapies. Ibrutinib demonstrated durable remissions, with 71% response rate and 75% progression-free survival at 26 months. The drug effectively inhibited BTK, leading to reduced lymphocyte counts and improved cytopenias. Ibrutinib was effective regardless of the dose and showed no significant difference in response based on mutation status of the immunoglobulin variable-region heavy-chain gene. The study supports the use of ibrutinib for relapsed CLL, with potential for monotherapy. Ongoing trials are evaluating its efficacy in combination with other agents.