Patients with chronic lymphocytic leukemia (CLL) harboring deletion 17p (del17p) cytogenetic abnormalities are associated with poor prognosis, and show suboptimal responses to chemoimmunotherapy, underscoring the need for novel treatment strategies. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase (BTK) inhibitor that is approved for treatment of patients with CLL who have received ?1 prior therapies, and for patients with a del17p cytogenetic abnormality.1 Stilgenbauer and colleagues reported the impact of baseline genetic features and prognostic factors on the efficacy and survival outcomes in the phase 2 RESONATE-17 study (PCYC-1117) of ibrutinib therapy in patients with del17p CLL/small lymphocytic leukemia (SLL), in which ibrutinib demonstrated high antileukemia activity.2,3
In this analysis, the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed by subgroup using the primary analysis data set. In addition to the presence of del17p cytogenetic abnormality in all patients, the baseline cytogenetic profile of the overall patient cohort (N = 144) included del11q (16%), del13q (74%), and trisomy 12 (17%). Of the 116 patients with valid baseline genomic samples, 84% had unmutated immunoglobulin variable heavy-chain region genes, and relevant genomic abnormalities included tumor protein 53 (92%), ataxia-telangiectasia mutated (14%), BIRC3 (3%), NOTCH1 (16%), and splicing factor 3B subunit 1 (27%). At a median follow-up of 11.5 months, ORR, including partial response with lymphocytosis (PR-L) for all patients, was 83% (17% PR-L), with 12-month PFS of 79%, and 12-month OS of 84% (median PFS and OS were not reached). Serious adverse events occurred in 40% of patients, 38% of which were grade ?3. When assessed by baseline characteristics, cytogenetics, and genomic variants, there were no substantial differences in ORR, 12-month PFS, and 12-month OS.
Based on these results, the authors concluded that ibrutinib showed remarkable clinical activity and improved survival outcomes in the high-risk del17p patient population regardless of baseline cytogenetic aberrations or genomic variants.
