Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia

We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized chronic lymphocytic leukem...

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Published in:	Blood advances Vol. 6; no. 11; pp. 3440 - 3450
Main Authors:	Barr, Paul M., Owen, Carolyn, Robak, Tadeusz, Tedeschi, Alessandra, Bairey, Osnat, Burger, Jan A., Hillmen, Peter, Coutre, Steve E., Dearden, Claire, Grosicki, Sebastian, McCarthy, Helen, Li, Jian-Yong, Offner, Fritz, Moreno, Carol, Zhou, Cathy, Hsu, Emily, Szoke, Anita, Kipps, Thomas J., Ghia, Paolo
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 14.06.2022 American Society of Hematology
Subjects:	Adenine - analogs & derivatives Chlorambucil - adverse effects Clinical Trials and Observations Follow-Up Studies Humans Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Leukemia, Lymphocytic, Chronic, B-Cell - genetics Piperidines Pyrazoles - adverse effects Pyrimidines - adverse effects Treatment Outcome
ISSN:	2473-9529, 2473-9537, 2473-9537
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Summary:	We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized chronic lymphocytic leukemia (CLL) studies. Patients (≥65 years) with previously untreated CLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5-0.8 mg/kg ≤12 cycles (n = 133). With up to 8 years of follow-up (range, 0.1-96.6 months; median, 82.7 months), significant PFS benefit was sustained for ibrutinib vs chlorambucil (hazard ratio [HR], 0.154; 95% confidence interval [CI], 0.108-0.220). At 7 years, PFS was 59% for ibrutinib vs 9% for chlorambucil. PFS benefit was also observed for ibrutinib- vs chlorambucil-randomized patients with high-risk genomic features: del(11q) (HR, 0.033; 95% CI, 0.010-0.107) or unmutated immunoglobulin heavy chain variable region (HR, 0.112; 95% CI, 0.065-0.192). OS at 7 years was 78% with ibrutinib. Prevalence of adverse events (AEs) was consistent with previous 5-year follow-up. Ibrutinib dosing was held (≥7 days) for 79 patients and reduced for 31 patients because of AEs; these AEs resolved or improved in 85% (67 of 79) and 90% (28 of 31) of patients, respectively. With up to 8 years of follow-up, 42% of patients remain on ibrutinib. Long-term RESONATE-2 data demonstrate sustained benefit with first-line ibrutinib treatment for CLL, including for patients with high-risk genomic features. These trials were registered at www.clinicaltrials.gov as #NCT01722487 and #NCT01724346. •Long-term RESONATE-2 data show sustained PFS and OS benefits (medians not reached) for first-line ibrutinib treatment in patients with CLL.•Forty-two percent of patients continued ibrutinib for up to 8 years; dose management for AEs allowed patients continue to benefit from ibrutinib. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 Requests for data sharing may be submitted to Paul M. Barr (paul_barr@urmc.rochester.edu.).
ISSN:	2473-9529 2473-9537 2473-9537
DOI:	10.1182/bloodadvances.2021006434