February 2016, Vol. 5, No. 1
Ibrutinib a New Standard of Care for Elderly CLL Patients
Ibrutinib significantly reduced the risk of disease progression and death compared with standard treatment with chlorambucil in older treatment-naive patients with chronic lymphocytic leukemia (CLL). Ibrutinib achieved a 91% reduction in risk of disease progression and an 84% reduction in the risk of death compared with chlorambucil.
These results from RESONATE-2 suggest that ibrutinib could become a new standard of care for this group of patients who typically cannot tolerate the fludarabine/cyclophosphamide/rituximab chemoimmunotherapy regimen used in younger patients.
“This population is frequently frail and undertreated. Chlorambucil has been the standard of care. No other regimen has improved survival in the elderly,” said lead author Alessandra Tedeschi, MD, Azienda Ospedaliera Niguarda Ca’ Granda, Milan, Italy.
Ibrutinib is a first-in-class oral inhibitor of Bruton’s tyrosine kinase; it is approved by the FDA for the treatment of patients with CLL treated with more than 1 prior therapy and those who have 17p deletions. The study results are expected to lead to an expanded indication for up-front treatment of elderly patients.
RESONATE-2 is the first phase 3 direct comparison of ibrutinib versus chemotherapy in this older population (≥65 years). The study enrolled 269 CLL patients. Exclusion criteria included del(17p) and warfarin. Median age was 73 years; 70% of patients were older than 70 years. Forty-three patients crossed over to ibrutinib over the course of the trial.
Ibrutinib significantly prolonged progression-free survival (PFS), as determined by an independent review committee; median PFS was not reached in the ibrutinib group versus 18.9 months in the chlorambucil group (P <.001) at a median of 18.4 months of follow-up.
Ibrutinib significantly prolonged overall survival (OS), with an estimated OS of 98% at 24 months versus 85% with chlorambucil (P = .001).
Overall response rate was also significantly superior with ibrutinib versus chlorambucil: 86% versus 35%, respectively (P <.001).
The most common adverse events associated with ibrutinib were diarrhea (42%), fatigue (30%), cough (22%), and nausea (22%). The most common adverse events associated with chlorambucil included nausea (39%), fatigue (38%), neutropenia (23%), and vomiting (20%).
Grade 3 hypertension was reported in 14% of ibrutinib patients. Hypertension was treated with antihypertensive medications, and no dose reduction or treatment discontinuation was needed. Atrial fibrillation was reported in 6% of patients in the ibrutinib arm (grade 2 in 6 patients, grade 3 in 2 patients); 2 of these patients discontinued treatment; and dose modifications were not needed for the other 4 patients.
Adverse events leading to treatment discontinuation were reported in 9% in the ibrutinib arm and in 23% of those treated with chlorambucil. During 18.4 months of follow-up, 3 deaths were reported in the ibrutinib arm and 17 in the chlorambucil arm. No deaths were reported in patients who progressed on ibrutinib during follow-up.
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