ORLANDO – Ibrutinib monotherapy was superior to chlorambucil with regard to progression-free survival, overall survival, overall response rate, event-free survival, and hematologic improvement in treatment-naïve older patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), a study presented at the American Society of Hematology (ASH) 57th Annual Meeting & Exposition and published in The New England Journal of Medicine has shown.1
“At the time this study was designed, chlorambucil was the standard of care in older patients with CLL,” said one of the study’s authors, Alessandra Tedeschi, MD, of Azienda Ospedaliera Niguarda Cà Granda in Milan, Italy.
For the open-label, phase 3 RESONATE-2 trial, researchers enrolled 269 patients with treatment-naïve CLL/SLL and randomly assigned them to receive ibrutinib 420 mg orally daily until disease progression or chlorambucil 0.5 mg/kg (maximum 0.8 mg/kg) on days 1 and 15 of each 28-day cycle for up to 12 cycles. Patients were not included if they had del17p gene mutations. “Patient characteristics were well-balanced between the 2 arms,” Dr Tedeschi noted.
Results showed that median progression-free survival as assessed by an Independent Review Committee was 18.9 months with chlorambucil and had not yet been reached with ibrutinib, corresponding to a reduction in the risk of progression or death by 84% by ibrutinib compared with chlorambucil (HR, 0.16; 95% CI, 0.09 – 0.28; P < .001) with a median follow-up of 18.4 months.
Researchers found that the 18-month progression-free survival rate was 90% with ibrutinib and 52% with chlorambucil and the 24-month overall survival rate was 98% and 85%, respectively. Ibrutinib treatment was associated with an 82% overall response rate vs 30% with chlorambucil (P < .001) at 18 months, with a trend toward increased rates of complete response.
“Ibrutinib significantly prolonged overall survival,” Dr Tedeschi said.
The study also demonstrated that ibrutinib significantly improved hematologic function in terms of hemoglobin and platelet improvements.
In regard to safety, “the most frequent adverse events associated with ibrutinib treatment were diarrhea, fatigue, cough, and nausea,” Dr Tedeschi said.
Of note, the incidence of hypertension, including grade 3 hypertension, was higher in the ibrutinib arm, but was well-managed with medication. Overall, however, adverse events leading to discontinuation were less common with ibrutinib than with chlorambucil.
“Ibrutinib showed favorable benefit-risk profile as first-line treatment of patients with CLL/SLL versus traditional chemotherapy,” Dr Tedeschi concluded.
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Due to the positive findings, a supplemental New Drug Application has been submitted to the U.S. Food and Drug Administration for the use of ibrutinib in patients with treatment-naïve CLL.
Ibrutinib is a first-in-class, oral, Bruton’s tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with CLL who have received 1 or more prior therapies for del17p CLL, including in the first-line setting.
- Tedeschi A, Barr PM, Robak T, et al. Results from the international, randomized phase 3 study of ibrutinib versus chlorambucil in patients 65 years and older with treatment-naïve CLL/SLL (RESONATE-2TM). Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.