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Ibrutinib in Combination with Rituximab is Well Tolerated and Induces a High Rate of Durable Remissions in Patients with High-Risk Chronic Lymphocytic Leukemia: New, Updated Results of a Phase 2 Trial in 40 Patients

Based on phase 1/2 trials, single-agent ibrutinib induces an overall response rate (ORR) of 71% in relapsed chronic lymphocytic leukemia (CLL).1 To enhance responses to ibrutinib in patients with high-risk CLL, a phase 2 study of ibrutinib in combination with rituximab was conducted. Burger and colleagues provided an update of this phase 2 single-center clinical trial after a median follow-up of 14 months.2

A total of 40 patients were treated with ibrutinib once daily throughout the study, while rituximab was given weekly for the first 4 weeks (cycle 1), followed by monthly administration until cycle 6, when patients continued on ibrutinib monotherapy. The study inclusion criteria required high-risk disease (treated or untreated), progression-free survival (PFS) less than 36 months after the first-line chemoimmunotherapy, or relapsed CLL with deletion 11q.2

At a median follow-up of 14 months, 32 of the 40 patients continued treatment with ibrutinib therapy without disease progression, including 16 of 20 patients with high-risk cytogenetics.

Among the 39 patients evaluable for response assessment, the ORR was 95%; 34 patients (87%) achieved partial remission and 3 patients (8%) achieved complete remission. Among the 20 patients with deletion 17p or TP53 mutation, the ORR was 90%.2

Of the 8 patients who discontinued treatment prematurely, 3 patients died of unrelated infectious complications; 1 patient died of unrelated organ failure; 2 patients had possible ibrutinib-related toxicity; 1 patient had progressive disease; and 1 patient proceeded to stem cell transplantation.2

Treatment was generally well tolerated, with infectious complications being the most common adverse events (AEs). Possibly related grade 3 AEs included mucositis and peripheral neuropathy. Quality of life questionnaires revealed significantly improved overall health and quality of life after 6 months of treatment with the ibrutinib combination, which corresponded with a significant weight gain at 3 months and 6 months.2

Burger and colleagues concluded that ibrutinib in combination with rituximab is safe and well tolerated in patients with high-risk CLL. In addition, the combination induces high rates of durable responses; the redistribution lymphocytosis resolved more rapidly and completely with ibrutinib plus rituximab compared with ibrutinib monotherapy, resulting in higher ORR. Furthermore, responses were associated with significant improvements in the quality of life. Whether the addition of rituximab to ibrutinib therapy results in longer PFS and overall survival will be addressed in an upcoming randomized trial of ibrutinib monotherapy versus the combination in relapsed or refractory CLL.2


  1. Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42.
  2. Burger JA, Keating MJ, Wierda WG, et al. Ibrutinib in combination with rituximab is well tolerated and induces a high rate of durable remissions in patients with high-risk chronic lymphocytic leukemia (CLL): new, updated results of a phase II trial in 40 patients. Blood. 2013 122(21). Abstract 675.
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Last modified: August 30, 2021