Five-Year Outcomes With Front-Line Ibrutinib in CLL
Posted: Tuesday, November 12, 2019
With median 5-year follow-up results of the phase III RESONATE-2 trial calculated, single-agent ibrutinib continues to demonstrate a significant, durable clinical benefit in older patients with chronic lymphocytic leukemia (CLL), and no new safety signals have emerged. The 1:1 randomized phase III trial was designed to compare first-line ibrutinib with chlorambucil in 269 patients with CLL 65 years or older, including those with high-risk prognostic features (TP53 mutation, del[11q], and/or unmutated IgHV), noted Jan A. Burger, MD, PhD, of MD Anderson Cancer Center, Houston.
“This is the longest follow-up report of [CLL] patients receiving first-line treatment with a [Bruton’s tyrosine kinase] inhibitor in a phase III study to date,” noted the team in Leukemia. Of the patients initially randomly assigned to the ibrutinib arm, 58% continue to receive the agent.
At 5 years, progression-free survival was 70% versus 12% in the ibrutinib and chlorambucil arms, respectively, and the overall survival rate was 83% versus 68%. “Ibrutinib benefit was also consistent in patients with a high prognostic risk,” emphasized Dr. Burger and colleagues. The investigator-assessed overall response rate was 92% with ibrutinib, and adverse events actually decreased over time. Because most patients with CLL are elderly, “treatments with a tolerable safety profile in long-term use are essential,” pointed out the authors.
In real-world studies of patients receiving first-line CLL treatment, including RESONATE-2–ineligible patients (ie, aged < 65 years or having del[17p]), response rates to ibrutinib (71%–82% vs. 92% in RESONATE-2) and the proportion of treatment discontinuations due to adverse events (51%–63% vs. 52% in RESONATE-2) were comparable.
Novel agents continue to be developed for CLL, stated Dr. Burger and co-investigators, but “long-term data [like these] are crucial to inform practice.”
Disclosure: The full disclosures of study authors can be found at nature.com.