FDA Approves Label Expansion for Leukemia Drug

The FDA recently updated ibrutinib (Imbruvica) Prescribing Information (PI) to include overall survival data from a pair of phase 3 clinical trials in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The update was based on data from the RESONATE-2 trial that showed Imbruvica caused significant improvement in previously untreated CLL and SLL patients, compared with chemotherapy.

“This update helps to affirm the established efficacy, safety and tolerability of this therapy for treatment of patients with CLL/SLL, both as a monotherapy or in combination with other agents,” said RESONATE-2 lead study investigator Jan Burger, MD, PhD. “It reflects the growing body of clinical evidence supporting this therapy as a potential treatment option for people living with CLL/SLL.”

The randomized, multi-center, open label, phase 3 study enrolled 269 treatment naïve patients with CLL or SLL, aged 65-years or older.

Randomized patients received either 420-mg orally of Imbruvica once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles.

Chlorambucil started at 0.5 mg/kg in cycle 1 and increased based on tolerability in cycle 2 by increments of 0.1 mg/kg with a maximum of 0.8 mg/kg.

The primary endpoint was progression free survival (PFS) as assessed by the Independent Review Committee.

Additionally, a supplemental overall survival analysis that included 41% of patients in the chlorambucil group who moved over to receive Imbruvica after progressing, showed a statistically significant 56% reduction in the risk of death after the median follow-up of 28.1 months (HR 0.44 [95% CI, 0.21, 0.92]).

The label now also includes data from the HELIOS trial that provided the first ever data on Imbruvica in combination with bendamustine and rituximab (BR) in relapsed and refractory CLL and SLL patients.

The phase 3, randomized, multi-center, double-blind, study enrolled 578 CLL/SLL patients who received at least 1 prior systemic therapy.

Randomized patients received either Imbruvica or placebo once daily until the disease progressed or unacceptable toxicity with 6 cycles of BR.

The HELIOS study met its primary endpoint, showing the combination of Imbruvica plus BR was associated with an 80% reduced risk of progression or death (HR=0.20 [95% CI, 0.15, 0.28]) compared with placebo plus BR.

Median PFS was not met in the Imbruvica plus BR group, compared with 13.3 months in the placebo plus BR group (95% CI, 11.3, 13.9).

“We are pleased the FDA has added the survival data observed with Imbruvica as a first-line therapy for CLL to its Prescribing Information and that the indication has been expanded to include patients with SLL,” said Danelle James, MD, MS, Head of Oncology at Pharmacyclics. “Moreover, the positive results seen in the HELIOS study provide additional evidence supporting the compelling safety and efficacy seen with Imbruvica in CLL and SLL patients. We believe the Imbruvica label is very strong for the treatment of certain hematologic malignancies and is now reinforced not only by data evaluating its use as a single agent, but also in combination with other commonly used chemotherapy regimens.”