Ibrutinib, an investigational agent that targets Bruton’s tyrosine kinase (BTK) to combat chronic lymphocytic leukemia (CLL), showed promising results in two phase II studies presented at the annual meeting of the American Society of Hematology (ASH), held in Atlanta, Georgia, December 8-11, 2012.

As explained in an ASH statement, primary treatment for CLL includes a combined chemotherapy-based regimen with fludarabine and cyclophosphamide, along with the immune therapy rituximab. Rituximab is generally not well-tolerated among elderly patients; nearly 70% of persons with CLL are aged 65 years and older. In addition, unlike ibrutinib, which selectively targets leukemia cells while leaving normal cells unharmed, rituximab compromises the immune system by attacking normal cells along with the cancerous targets.

In one study, led by John C. Byrd, MD, of the Division of Hematology at The Ohio State University in Columbus, Ohio, ibrutinib monotherapy was found to be highly active and well-tolerated in a total of 116 persons with CLL. The group consisted of patients with relapsed/refractory disease (persons who had received two or more prior therapies), including those with high-risk disease (persons who had relapsed within two years of treatment), as well as patients aged 65 years and older who had undergone no prior treatment.

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The majority (71%) of the previously treatment-naïve elderly patients experienced a complete or partial response at one of two oral dosing regimens (420 mg/day or 840 mg/day). The same was observed for 67% of the relapsed patients and 50% of the high-risk patients.

After 22 months of follow-up, there was no disease progression in 96% of the previously treatment-naïve patients or in 76% of the relapsed and high-risk patients. Only nonsevere side effects occurred, including diarrhea, fatigue, chest infection, rash, nausea, joint pain, and infrequent and transient low blood counts.

In the other study, Jan A. Burger, MD, PhD, of the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, Texas, and colleagues combined ibrutinib with rituximab. The investigators sought to accelerate and improve responses in their group of 40 patients with high-risk CLL (median age 65 years; range 35–82 years). Participants had undergone a median of two prior therapies before receiving the current treatment, which consisted of ibrutinib 420 mg/day and weekly rituximab for 4 weeks, then daily ibrutinib plus monthly rituximab until month 6, followed by ibrutinib monotherapy.

At 4 months of follow-up, 38 of the 40 patients continued on therapy without disease progression; overall response rate was 85%. Half of the participants were evaluable for early response; 17 of those 20 patients achieved partial remission.

All patients reported improvements in health and quality of life, with little severe toxicity. Most cases of early lymphocytosis that occurred due to the ibrutinib-induced shift of CLL cells from lymph node tissues into the blood peaked early and resolved. The duration of lymphocytosis was shorter with combination therapy than with ibrutinib alone; the investigators noted that this was likely attributable to the addition of rituximab.