LIVING LONGER IN 1L CLL1,2

RESONATE™-2: Data1,2

Phase 3, multicenter, open-label trial of 1L CLL/SLL patients (N=269) ≥65 years of age who were randomized 1:1 to IMBRUVICA® 420 mg once daily until disease progression or unacceptable toxicity (n=136) or chlorambucil (n=133) for up to 12 cycles. Patients with del17p were excluded. The primary endpoint was PFS as assessed by an IRC per iwCLL criteria (primary analysis). OS was a secondary endpoint. Patients with IRC-confirmed disease progression were enrolled in an extension study (long-term follow-up), providing valuable RESONATE™-2 data, and second-line treatment per investigator’s choice (including IMBRUVICA® for patients progressing on chlorambucil). 

Results for RESONATE™-2 Clinical Trials in CLL

RESONATE™-2 primary analysis1,2

  • HR=0.44 (95% CI: 0.21, 0.92) (secondary endpoint)
  • Median follow-up of 28.1 months
  • 41% of chlorambucil-treated patients crossed over to IMBRUVICA® upon disease progression
  • HR=0.16 ([95% CI: 0.09, 0.28]; P<0.001) (IRC-assessed primary endpoint)
  • Median follow-up of 18.4 months
  • Median PFS with IMBRUVICA® was not estimable vs 18.9 months (95% CI: 14.1, 22.0) with chlorambucil

WITH UP TO 8 YEARS OF FOLLOW-UP DATA3

RESONATE™-2: Long-term analysis

8-year RESONATE™-2 long-term efficacy results are not included in the Prescribing Information for IMBRUVICA®. The timing for long-term follow-up was not prespecified, and the analysis was descriptive in nature. 

  • Median follow-up of RESONATE™-2 was 7.4 years (88.5 months; range, 0.1-96.6 months)

Long-term OS analysis3

  • Median OS was not reached for IMBRUVICA® patients after up to 8 years of follow-up3

Long-term PFS analysis (investigator assessed)3

  • Median PFS has not yet been reached for patients in the IMBRUVICA® arm (95% CI: 82.1, NE) vs 15 months (95% CI: 10.2, 19.4) for patients in the chlorambucil arm after up to 8 years of follow-up3

WITH UP TO 8 YEARS OF FOLLOW-UP IN 1L CLL/SLL, INCLUDING HIGH-RISK

Descriptive subgroup analysis: OS of high-risk groups, including TP53 mutation, del11q, and unmutated IGHV4

  • RESONATE™-2 was not designed to test treatment effect in subpopulations and was not powered to show statistical differences among these subgroups
  • Subgroup analysis was not prespecified, is descriptive, and is not included in the USPI
  • No subgroups were adjusted for multiplicity, and there is no P value
  • Patients with del17p were excluded from the trial

High-risk OS analysis: long-term follow-up

  • Median follow-up of LTFU RESONATE™-2 was 7.1 years (84.9 months; range, 0.7-93.6 months)4

Primary analysis: forest plot4

8-year RESONATE™-2 long-term efficacy results are not included in the Prescribing Information for IMBRUVICA®. The timing for long-term follow-up was not prespecified, and the analysis was descriptive in nature.

Abbreviations

1L=frontline, BTKi=Bruton’s tyrosine kinase inhibitor, CI=confidence interval, CLL=chronic lymphocytic leukemia, del=deletion, HR=hazard ratio, I=IMBRUVICA®, IGHV=immunoglobulin heavy-chain variable region gene, IRC=independent review committee, iwCLL=International Workshop on Chronic Lymphocytic Leukemia, NE=not estimable, OS=overall survival, PD=progressive disease, PFS=progression-free survival, SLL=small lymphocytic lymphoma, TP53=tumor protein 53, uIGHV=unmutated immunoglobulin heavy-chain variable region gene.

References

1IMBRUVICA® (ibrutinib) Prescribing Information. 2Burger JA, Tedeschi A, Barr PM, et al; for the RESONATE-2 Investigators. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437. 3Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6(11):3440-3450. 4Data on file.