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Final Analysis from RESONATE: Up to Six Years of Follow-up on Ibrutinib vs Ofatumumab in CLL

The final analysis of the RESONATE study, with up to six years of follow-up, highlights the efficacy and safety of ibrutinib compared to ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Ibrutinib demonstrated significantly longer progression-free survival (PFS) and overall survival (OS) benefits, especially in high-risk patients. The study also noted the long-term tolerability of ibrutinib, with a decrease in adverse events over time.

Patient Features

Baseline characteristics showed similar high-risk features among patients randomized to ibrutinib (n = 195) or ofatumumab (n = 196), including del(17p), TP53 mutation, del(11q), unmutated IGHV, and complex karyotype. The majority in both arms were high-risk, defined by having any of the mentioned genetic abnormalities.

Progression-Free Survival

With a median follow-up of 74 months, the median PFS was 44.1 months for ibrutinib and 8.1 months for ofatumumab. Ibrutinib's PFS benefit was consistent across subgroups, including those with high-risk features. Notably, patients with del(11q) had a median PFS of 60.7 months with ibrutinib.

Overall Survival

Median OS was 67.7 months for ibrutinib and 65.1 months for ofatumumab. Adjusting for crossover, OS was significantly better for ibrutinib. Patients with del(17p) had a median OS of 61.8 months with ibrutinib.

Adverse Events

The most common treatment-emergent adverse events (AEs) with ibrutinib included neutropenia, thrombocytopenia, anemia, pneumonia, hypertension, urinary tract infection, diarrhea, and atrial fibrillation. The prevalence of grade ≥3 AEs decreased over time, except for hypertension.

Conclusion

The 6-year follow-up confirms the robust efficacy and safety of ibrutinib in relapsed or refractory CLL, including in high-risk patients. Continuous ibrutinib treatment offers significant PFS and OS benefits, with a manageable safety profile over extended periods.


Reference News

Final analysis from RESONATE: Up to six years of follow‐ ...

The RESONATE study's 6-year update confirms ibrutinib's efficacy in relapsed/refractory CLL, showing a median PFS of 44.1 months vs. 8.1 months for ofatumumab. Ibrutinib benefits all risk groups, including those with high-risk features, and maintains a favorable safety profile over time. ORR remains high at 91%, with CR/CRi rates increasing to 11%. Long-term treatment is well-tolerated, with most grade ≥3 AEs decreasing annually, except for hypertension.

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