Ibrutinib sustains efficacy in CLL at 4-year follow-up

Response rates

Dr Brown noted that, early on, there’s quite a significant rate of partial response with lymphocytosis observed in patients on ibrutinib.

This “diminishes dramatically,” she said, but about 5% of patients at 3 and 4 years still have ongoing lymphocytosis.

“Similarly, initially, there’s a very low rate of complete remission, which has risen steadily to 9% at this follow-up,” she said.

And the overall response rate is 91%.

Treatment exposure and toxicity

The median duration of ibrutinib treatment is 41 months, and 46% of patients continue on treatment. Twenty-seven percent of patients discontinued due to progression, and 12% because of adverse events (AEs).

Of the 53 patients who discontinued therapy, 14 had transformation as their primary reason, 9 with diffuse large B-cell lymphoma, 3 with Hodgkin disease, and 2 with prolymphocytic lymphoma.

The most frequent AEs leading to discontinuation included pneumonia (n=3), anemia (n=2), thrombocytopenia (n=2), diarrhea (n=2), and anal incontinence (n=2).

AEs leading to discontinuation decreased over time—6% in year 0 to 1 and 4% in years 2 to 3.

“The most frequent cumulative AEs are similar to what we’ve seen in most prior studies,” Dr Brown said, including diarrhea, fatigue, and cough.

In terms of grade 3 or higher AEs, about a quarter of patients had neutropenia, 17% had pneumonia, and 8% had hypertension.

Six percent of patients had major hemorrhage, and all-grade atrial fibrillation occurred in 11% of patients.

“Now, many of the grade 3 and higher AEs did decline over time during the study,” Dr Brown noted. “You can see this is quite evident for neutropenia as well as pneumonia, and all infections declined from year 1 to subsequent years.”

Hypertension, in contrast, has been fairly steady over the later years, she said, and atrial fibrillation is highest in the first 6 months but then continues at a low rate thereafter.

The investigators believe these long-term results demonstrate that ibrutinib is tolerable and continues to show sustained efficacy in previously treated and high-genomic-risk patients with CLL. In addition, no long-term safety signals have emerged.

This study was sponsored by Pharmacyclics, LLC, an AbbVie company.