Survival Benefits, Established Safety Profile of Single-agent Ibrutinib for CLL Reinforced in Long-term Phase 3 Study


Phase 3 data presented at the 2021 ASCO Annual Meeting have reinforced the long-term survival benefits and well-established safety profile of single-agent ibrutinib for patients with CLL.

Data from the RESONATE-2 study have reinforced the long-term survival benefits and well-established safety profile of single-agent ibrutinib (Imbruvica, Janssen) for patients with chronic lymphocytic leukemia (CLL), according to a presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. These long-term data from RESONATE-2 is the longest follow-up phase 3 data published for any Bruton tyrosine kinase (BTK) inhibitor to date.

“Ibrutinib was the first BTK inhibitor approved in Europe and has been used to treat more than 230,000 patients worldwide. It is now also the first BTK inhibitor to be studied as a fixed-duration combination treatment option,” said Edmond Chan, EMEA Therapeutic Area Lead Hematology, Janssen-Cilag Ltd, in a press release. “The latest data to be presented at ASCO reinforce the potential of ibrutinib as a foundational treatment option across the CLL landscape and add to the breadth of evidence regarding its efficacy and safety profile.”

During the RESONATE-2 study, investigators enrolled 269 previously untreated patients with CLL aged 65 years or older who had not presented with the del(17p) mutation. These patients were then randomly assigned to be administered continuous ibrutinib or chlorambucil for up to 12 cycles.

The investigators then conducted the follow-up over a period of up to 7 years. Based on the resulting long-term data, the progression-free survival (PFS) benefit of treatment with single-agent ibrutinib was found to be sustained (PFS hazard ratio [HR] 0.160 [95% CI: 0.111–0.230]).

At the follow-up point of 6.5 years, the investigators found that the median PFS with ibrutinib had not been reached, as 61% of patients treated with single-agent ibrutinib were alive and progression-free, whereas 9% of patients who were treated with chlorambucil were alive and progression-free.

Additionally, the PFS benefit for patients treated with ibrutinib was observed by the investigators as being present across all subgroups, including those with high-risk genomic features of TP53 mutation, unmutated IGHV, or 11q deletion (HR 0.091 [95% CI: 0.054–0.152]).

Furthermore, the complete response (CR) rate for patients treated with ibrutinib was found to increase to 34% over time, with 78% of patients treated with ibrutinib alive at 6.5 years. At the 7-year follow-up point, approximately half of patients were still receiving ibrutinib treatment as well.

The investigators also found that ibrutinib was well tolerated by patients as a long-term treatment with no new safety signals during the long-term study period. The rates of grade 3 or higher adverse effects (AEs) remained low for both hypertension (5-to-6-year interval: n=20; 6-to-7-year interval: n=15) and atrial fibrillation (5-to-6-year interval: n=7; 6-to-7-year interval: n=5).

During the 5- to-7-year interval, the investigators observed no grade 3 or higher major hemorrhage, with AEs of any grade leading to discontinuations in 3% (n=2) of patients from year 5 to 6, and no patients discontinuing ibrutinib due to AEs from year 6 to 7.

“The positive results from the CAPTIVATE study demonstrate the potential of ibrutinib and venetoclax, with complementary mechanisms of action, to provide deep responses with a once-daily, fixed-duration combination that can be administered in the outpatient setting for younger, fit patients,” said Craig Tendler, MD, vice president, clinical development and global medical affairs, oncology, Janssen Research & Development, in the press release. “The results from RESONATE-2 further support the long-term benefit of ibrutinib monotherapy in front line CLL for which the breadth and maturity of data continue to grow in support of this standard-of-care treatment and its impact on progression free and overall survival.”


IMBRUVICA® (ibrutinib)-Based Combination Regimen as a Fixed-Duration, First-Line Treatment for Chronic Lymphocytic Leukaemia Demonstrates High Rates of Disease Control. Beerse, Belgium: Janssen Pharmaceutical Companies; May 19, 2021. Accessed June 9, 2021.

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