Ibrutinib and acalabrutinib ± obinutuzumab are preferred first-line therapy options for all patients including in high-risk subgroups such as those with del(11q) or del(17p)/TP53 mutation and unmutated IGHV.

Eligible pts had TN CLL requiring treatment per iwCLL criteria and were aged ≥65 y or <65 y with coexisting conditions (CIRS score >6, creatinine clearance <70 mL/min)....PFS improvement with acalabrutinib + O or acalabrutinib vs O + Clb was consistent across subgroups examined including del(17p) (HR [95% CI]; 0.13 [0.04-0.46]; 0.20 [0.06-0.64]).

In 73 pts with del(17p) and/or TP53m, median PFS was 73.1 mo for A+O and NR for A vs 17.5 mo for O+Clb (HR: 0.28 and 0.23, respectively…With a median follow-up of 74.5 mo, the efficacy and safety of A+O and A monotherapy were maintained in pts with TN CLL, including in pts with high-risk genetic features. At 6 years of follow-up, PFS was significantly longer in pts treated with A+O vs A.

Data were pooled from CLL pts with higher-risk genomic features treated with A ± obinutuzumab (O) in 3 clinical studies...At 47.3 mo median follow-up (range 1.0–82.0), median PFS was not reached (NR) in TN pts with del(17p)/TP53m with A-based regimens; PFS rates at 48 mo suggest similar efficacy with A and A+O in TN pts with del(17p)/TP53m (76% and 77%, respectively) (Fig 1A)....In this pooled analysis of clinical trial data in 801 CLL pts with higher-risk genomic features, efficacy of A-based regimens led to high PFS and OS rates at a median follow-up of nearly 4