Ibrutinib has greater efficacy than ofatumumab as second-line therapy for chronic lymphocytic leukemia

by Bruce Sylvester – Ibrutinib has significantly outperformed ofatumumab as a second-line therapy for chronic lymphocytic leukemia (CLL), according to a Phase 3 study published on May 31, 2014  in the OnLine First edition of the New England Journal of Medicine/NEJM.

The investigators randomized 391 subjects to receive once-a-day oral ibrutinib (n=195) or the anti-CD20 antibody ofatumumab (n=196), a drug used currently as standard of care for CLL.

Median follow-up was 9.4 months.

The researchers reported that ibrutinib significantly increased progression-free survival as a second-line therapy for CLL compared to ofaumumab.

“At median follow-up, 86 percent of patients on ibrutinib had durable response and were continuing treatment with minimal side effects. This is remarkable, especially considering that standard CLL therapies typically produce a 35-40 percent response rate,” said lead investigator John C. Byrd, MD, hematology division director at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio.

At six months, 83 percent of subjects treated with ibrutinib had achieved progression-free survival compared to 49 percent on ofatumumab.

“Ibrutinib significantly prolonged progression-free survival, resulting in a 78 percent reduction in the risk of disease progression or death in patients treated with ibrutinib compared with ofatumumab,” adds Byrd. “We observed similar progression-free survival results regardless of age, clinical stage or unique factors such as genetic mutation status.”

As background, the authors noted that, in 2013, the same investigators reported data from a phase 1b/2 study of with relapsed CLL. Based on positive early response rates, the (US) FDA Data Monitoring Committee recommended that ofatumumab subjects in the trial be allowed to switch to the ibrutinib arm. Thereafter, 29 percent of subjects with confirmed disease progression on ofatumumab switched to ibrutinib.

At 12 months, overall survival among ibrutinib subjects was 90 percent compared to 81 percent for ofatumumab. And 43 percent of ibrutinib subjects achieved partial response to treatment compared with 4 percent of ofatumumab subjects.

“There is no question that ibrutinib far outperforms existing therapies we have for CLL, and we’re excited to see this drug improving the outcome for patients who were once considered incurable,” said Byrd.