RESONATE2 Update on First-Line Ibrutinib in Older Patients With CLL/SLL
Posted: Tuesday, August 13, 2019
In reportedly the longest follow-up to date from a phase III study of first-line Bruton’s tyrosine kinase–directed therapy, the updated findings of the RESONATE2 trial confirm that treatment with ibrutinib significantly improves progression-free and overall survival in older patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) compared with chlorambucil. After up to 66 months of follow-up, responses to ibrutinib improved over time with almost threefold more patients achieving complete response or complete response with incomplete marrow recovery. The results were presented the 2019 International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (Abstract 061).
After 5 years, “more than half of patients remain on long-term continuous ibrutinib treatment, and no new safety signals emerged,” stated Alessandra Tedeschi, MD, of the Niguarda Cancer Center, Milan, Italy, and colleagues.
The randomized, open-label, international study enrolled 269 patients at least 65 years old with previously untreated CLL or SLL without 17p deletion. The patients were randomly assigned to either continuous ibrutinib at 420 mg once daily or chlorambucil at 0.5 to 0.8 mg/kg for up to 12 cycles.
After a median follow-up of 60 months, superior progression-free survival was sustained for ibrutinib (70%) compared with chlorambucil (12%), and overall survival was better in the ibrutinib cohort (83% vs. 68%). Ibrutinib also significantly improved progression-free survival compared with chlorambucil in patients with unmutated immunoglobulin heavy chain variable region, 11q deletion, and a high-risk genomics subgroup. The overall response rate with ibrutinib, including partial response with lymphocytosis, was 92%; 58% of patients remain on treatment with ibrutinib.
The most common grade ≥ 3 adverse events reported with ibrutinib included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), hyponatremia (6%), atrial fibrillation (5%), and cataract (5%), with the rates of most events decreasing over time. After discontinuing ibrutinib, most patients responded to subsequent CLL therapies, including chemoimmunotherapy and alternate kinase inhibitors.
Disclosure: The study authors’ disclosure information can be found at lymphcon.ch.