Study bolsters support of ibrutinib as second-line therapy in CLL treatment

June 9, 2014

Ibrutinib (Imbruvica) outperformed ofatumumab as a second-line therapy, for the treatment of relapsed chronic lymphocytic leukemia (CLL), according to a multicenter interim study published in the OnLine First edition of the New England Journal of Medicine.

Ibrutinib (Imbruvica) outperformed ofatumumab as a second-line therapy, for the treatment of relapsed chronic lymphocytic leukemia (CLL), according to a multicenter interim study published in the OnLine First edition of the New England Journal of Medicine.

In the head-to-head phase 3 trial comparing ibrutinib to ofatumumab, patients were randomly assigned to receive once-a-day oral ibrutinib or the anti-CD20 antibody ofatumumab, which is considered part of the current standard of care for CLL. Of the 391 patients enrolled in the phase 3 study, 195 were randomly assigned to ibrutinib and 196 to ofatumumab. Median follow-up was 9.4 months and showed that ibrutinib significantly lengthened progression-free survival (PFS) as a second-line therapy for CLL before anything else is used.

At median follow-up, 86% of patients on ibrutinib had durable response and were continuing treatment with minimal side effects. Standard CLL therapies typically reportedly produce a 35% to 40% response rate. At 6 months, 83% of patients treated with ibrutinib experienced progression-free survival compared to 49% of patients on ofatumumab. Ibrutinib significantly prolonged PFS, resulting in a 78% reduction in the risk of disease progression or death in patients treated with ibrutinib compared with ofatumumab.

“This is the first randomized study to show that an orally, well-tolerated targeted therapeutic [ibrutinib] produces durable remissions, improves survival in the majority of CLL patients treated with this as compared to a standard comparator, ofatumumab,” according to John C. Byrd, MD, principal investigator of the study and hematology division director at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James.)

“For the first time this also shows that with a single targeted therapeutic one can produce durable remissions in the majority of patients in the absence of a common genetic aberration-as seen in chronic myeloid leukemia,” Dr Byrd said. “This study will establish ibrutinib as the best treatment for relapsed CLL and cause it to be used before other treatments.”

 

Ibrutinib is the first drug designed to target Bruton’s tyrosine kinase (BTK), a protein essential for CLL-cell survival and proliferation. CLL, the most common form of leukemia, causes a gradual increase in white blood cells called B lymphocytes, or B cells, according to an Ohio State University press release.

According to the National Cancer Institute, 15,680 Americans ​were diagnosed with CLL and 4,580 died from the disease in 2013.

In 2013, Dr Byrd and colleagues reported findings from a phase 1b/2 study of 85 patients with relapsed CLL patients on ibrutinib in the New England Journal of Medicine.  Based on positive early response rates, the Data Monitoring Committee recommended patients be given option to switch to the ibrutinib arm of the study. At that time, 29% of patients with confirmed disease progression on ofatumumab crossed over to the ibrutinib arm of the study.

At 12 months, the overall survival rate among patients treated with ibrutinib was 90% compared to 81% in ofatumumab arm.  Additionally, 43% of patients on ibrutinib achieved partial response to treatment compared with just 4% of patients receiving ofatumumab.

Phase 3 studies are currently under way at The OSUCCC – James and affiliated cancer centers to determine whether ibrutinib is effective as a first-line therapy in CLL, and in other blood cancer treatment challenges such as reducing graft versus host disease in bone marrow transplant patients.

 

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