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Imbruvica (Ibrutinib) Improves Survival in Treatment-Naïve Leukemia Patients in Late-Stage Trial

Treatment achieves primary and secondary survival endpoints

Imbruvica (ibrutinib, Pharmacyclics/Janssen Biotech) has improved progression-free survival (PFS) and multiple secondary endpoints, including overall survival (OS) and the overall response rate (ORR), in treatment-naïve patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the final analysis of the phase III RESONATE-2 trial.

RESONATE-2 was a randomized, open-label study comparing ibrutinib and chlorambucil in 269 treatment-naïve CLL/SLL patients aged 65 years or older. CLL patients with deletion of the short arm of chromosome 17 (del 17p CLL) were excluded from the trial since single-agent chlorambucil is not an effective therapy in this population.

 The patients were randomly assigned to receive either ibrutinib 420 mg once daily until progression or toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg based on tolerability in cycle 2. The study’s primary endpoint was PFS, as assessed by an independent review committee, with modification for treatment-related lymphocytosis. Key secondary endpoints included OS, ORR, and safety.

Imbruvica (ibrutinib) is currently approved for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy; for all CLL patients (including treatment-naïve) who have del 17p, a genetic mutation that occurs when part of chromosome 17 has been lost; and for all patients (including treatment-naïve) with Waldenström’s macroglobulinemia. Imbruvica is also approved for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Accelerated approval was granted for the MCL indication based on the overall response rate. Continued approval for this indication may be contingent on the verification of clinical benefit in confirmatory trials.

Ibrutinib is a first-in-class, oral, once-daily therapy that inhibits Bruton’s tyrosine kinase (BTK). BTK is a signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells. Ibrutinib blocks signals that tell malignant B cells to multiply and spread uncontrollably.

 Sources: PR Newswire; June 4, 2015; and Imbruvica Prescribing Information; January 2015.


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