Suggested treatment regimens...CLL/SLL with del(17p)/TP53 mutation…first line therapy…preferred regimen...Acalabrutinib ± obinutuzumab

Estimated 48-month PFS rates overall were 87.0% for acalabrutinib-obinutuzumab, 77.9% for acalabrutinib, and 25.1% for obinutuzumab-chlorambucil. In the acalabrutinib-obinutuzumab and acalabrutinib monotherapy arms, 48-month PFS rates were 74.8% and 76.2%, respectively, for patients with del(17)(p13.1) and/or mutated TP53, and 85.7% and 77.1% for patients with unmutated IGHV...The ORR was significantly higher with acalabrutinib-obinutuzumab (96.1% [n = 172/179]; 95% CI, 92.1, 98.1) versus obinutuzumab-chlorambucil (82.5% [n = 146/177]; 95% CI, 76.2, 87.4; P < 0.0001; Supplementary Fig. 3A). The ORR with acalabrutinib (89.9% [n = 161/179]; 95% CI, 84.7, 93.5) also was significantly higher versus obinutuzumab-chlorambucil (P = 0.035).Based on these updated results, ELEVATE-TN shows continued efficacy at 4 years and a significant PFS benefit in the acalabrutinib-containing arms regardless of high-risk status.

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.