Phase III RESONATE-2 Study Confirms Sustained PFS Benefit of Imbruvica in CLL

Phase III RESONATE-2 Study Confirms Sustained PFS Benefit of Imbruvica in CLL
Phase III RESONATE-2 Study Confirms Sustained PFS Benefit of Imbruvica in CLL

Johnson & Johnson, announced results from the final analysis of the Phase III RESONATE-2 study, demonstrating a significant and sustained progression-free and overall survival benefit in patients with chronic lymphocytic leukemia (CLL). previously untreated patients receiving Imbruvica (ibrutinib) as monotherapy versus chlorambucil, with a follow-up of up to 10 years. The data were presented in a poster at the European Hematology Association (EHA) Congress 2024, which took place in Madrid from June 13 to 16, 2024.

When ibrutinib was first introduced more than ten years ago“changed the course of treatment for chronic lymphocytic leukemia (CLL), and today remains an essential element of the standard treatment of patients with B-cell malignancies,” says Alessandra Tedeschi, from the Niguarda Hospital in Milan, Italy. , clinical study investigator. “The final analysis of the RESONATE-2 study confirms that the favorable benefit-risk profile of ibrutinib is maintained over time, with the longest follow-up data of any targeted treatment in CLL, and demonstrates its potential to allow “Patients diagnosed with CLL currently consider the possibility of a normalized life expectancy,” he adds.

Phase III RESONATE-2 Study Evaluated 269 Previously Untreated CLL Patients, aged 65 years or older, who were randomly assigned to receive single-agent ibrutinib or chlorambucil for up to 12 cycles. With follow-up of up to 10 years, patients treated with ibrutinib demonstrated a significant and sustained benefit in progression-free survival (PFS) versus patients treated with chlorambucil. Median PFS was 8.9 years in the ibrutinib arm versus 1.3 years in the chlorambucil arm. The PFS benefit was significantly greater for patients treated with ibrutinib in all subgroups, including those with high-risk genomic features: TP53 mutation, wild-type IGHV, or 11q deletion. With follow-up of up to 10 years, the median OS with ibrutinib had not been reached, and at nine years the OS rate was 68 percent. At 10 years, 27 percent of study patients were still taking ibrutinib, with a median treatment duration of 6.2 years.

Ibrutinib was well tolerated as long-term treatment and no new safety alerts emerged. Adverse event (AE) rates of interest during years 8-9 and 9-10 were 28 percent and 26 percent, respectively, for hypertension, and eight percent and nine percent, respectively, for atrial fibrillation. Over the entire duration of the study, 34 of 136 patients (25 percent) receiving ibrutinib experienced AEs of any grade that led to a dose reduction, of which 28 of 34 patients (82 percent) resolved. all AAs. AEs of any grade led to ibrutinib discontinuation in 33 percent of patients throughout the study duration, in 13 percent of patients at years eight and nine, and in 7 percent of patients at years nine and 10. No patients discontinued ibrutinib due to disease progression at years nine and ten.

New pooled data from three randomized Phase 3 trials of first-line ibrutinib treatment in patients with CLL were presented at the EHA meeting. The pooled analysis included the RESONATE-2 and iLLUMINATE studies, which studied ibrutinib as a single agent or in combination with rituximab or obinutuzumab, respectively. In the pooled studies, a combined total of 600 patients aged 31 to 89 years were treated with ibrutinib.. With a median follow-up of 49.7 months, OS was comparable between patients treated with ibrutinib and the age-matched European general population using survival probability by age group from the 2019 life tables published by the World Health Organization. health.

Estimated OS was also comparable for the subgroup of ibrutinib-treated patients aged 65 years and older. The estimated OS was similar to that of the age-matched European population when extrapolated by patients receiving single-agent ibrutinib or the combination of ibrutinib and rituximab or obinutuzumab. These data are consistent with a previous analysis of the US population, presented at the 2023 American Society of Hematology (ASH) Annual Meeting.

“These results suggest that treatment with ibrutinib, with or without the addition of a CD20 antibody, offers European patients with chronic lymphocytic leukemia a standard life expectancy, comparable to that of their fellow citizens“says Edmond Chan, surgical specialist for Europe, the Middle East and Africa in the Hematology therapeutic area of ​​Johnson & Johnson Innovative Medicine. “Our goal has been to change what a blood cancer diagnosis means, and with ibrutinib, we are proud to be at the forefront and lead the way in medicine,” she adds.

A real-world evidence poster provided additional information on the potential effect of ibrutinib dose reductions on treatment duration (TD) and Time to next treatment (TST) in patients treated with ibrutinib versus acalabrutinib in first-line treatment. The findings suggest that ibrutinib dose reductions may be an effective strategy to manage tolerability while maintaining clinical efficacy.

Among the 286 patients who initiated first-line treatment with single-agent ibrutinib at a dose of 420 mg/day, 15 percent had a dose reduction; 171 patients started first-line treatment with single-agent acalabrutinib. The mean time elapsed between the start of first-line treatment and the index date was 167 days in each cohort. The median post-index follow-up time was 425 and 221 days for the ibrutinib and acalabrutinib dose reduction cohorts, respectively. The median duration of first-line treatment (including treatment-free interval) was 21.3 and 11.1 months for the ibrutinib and acalabrutinib dose reduction cohorts, respectively. A total of 37 percent and 35 percent of patients discontinued treatment in the ibrutinib and acalabrutinib dose reduction cohorts, respectively; median DT was not reached in the ibrutinib dose reduction cohort and was 9.5 months in the acalabrutinib cohort.

TD was longer in the ibrutinib dose reduction cohort than in the acalabrutinib cohort. A total of 16 percent and 17 percent of patients in the ibrutinib and acalabrutinib dose reduction cohorts received the next line of treatment during the follow-up period, respectively; the median TST was not reached in either cohort. TST was longer for the ibrutinib dose reduction cohort. These real-world tests are subject to the potential confounding bias that is often associated with observational research.

“These latest findings add to the strong data supporting ibrutinib, the most extensively studied Bruton’s tyrosine kinase inhibitor in the world, and the cornerstone of care in chronic lymphocytic leukemia,” said Mark Wildgust, Vice President of Business Affairs. Johnson & Johnson Innovative Medicine Global Doctors. “Reflecting on the decade since its first approval, ibrutinib stands as a testament to the progress that has come to redefine what it means to live with B-cell malignancies.“, he reiterates.


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