Living longer with CLL1,2

RESONATE™-2 Primary Data1,2

Study Design: Phase 3, multicenter, open-label trial of patients with 1L CLL/SLL (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).1,2

95%
OS

Estimated 2-Year OS Rate with IMBRUVICA®1,2

(95% CI: 89, 97) vs 84% with chlorambucil (95% CI: 77, 90)
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
90%
PFS

Estimated 18-Month PFS Rate with IMBRUVICA®1,2

vs 52% with chlorambucil
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
My doctor decided to prescribe IMBRUVICA®...and I'm still here
Eddie, an IMBRUVICA® patient living with CLL

WITH UP TO 10 YEARS OF FOLLOW-UP DATA3,4

RESONATE™-2: Long-term analysis

Data Limitations: 10-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.

  • The median follow-up for patients in the IMBRUVICA® arm for all efficacy endpoints was 9.6 years (115.0 months [range 0.1-122.8])3,4
68%
OS

Estimated OS at 9 years with IMBRUVICA®4

50%
PFS

Estimated PFS at 9 years with
IMBRUVICA® vs 4% with chlorambucil4

Long-term OS analysis4

  • Median OS was not reached in the IMBRUVICA® arm4

Long-term PFS analysis4

  • With up to 10 years of follow-up, median PFS for IMBRUVICA® was 8.9 years (95% CI: 7.0, NE) vs 1.3 years (95% CI: 0.9, 1.6) with chlorambucil4
  • For patients in the chlorambucil arm, median follow-up was 5.6 years (66.7 months [range 0.1-118.4 months])3

HIGH-RISK DATA:  UP TO 10 YEARS OF FOLLOW-UP IN 1L CLL3

Long-term OS data in high-risk patients

Descriptive subgroup analysis: OS data for patients with high-risk mutations, including TP53 mutation, del11q, and unmutated IGHV5

  • The RESONATE™-2 long-term subgroup analysis was not prespecified, is descriptive, and is not included in USPI
  • RESONATE™-2 was not designed to test treatment effects in subpopulations and was not powered to show statistical differences among these subgroups
  • No subgroups were adjusted for multiplicity, and there is no P-value
  • Patients with del17p were excluded from the trial
  • RESONATE™-2, all subgroups were prespecified in the protocol, except for IGHV mutation status, which was exploratory.

Descriptive subgroup OS analysis in high-risk groups

IMBRUVICA® (ibrutinib) 9-year OS rate data in high-risk patients with CLL/SLL in RESONATE™-2 trial
  • Median follow-up of high-risk group LTFU RESONATE™-2 was 9.6 years
    (115.0 months; range, 0.1–122.8 months)3

Primary analysis: Forest plot5

IMBRUVICA® (ibrutinib) RESONATE™-2 trial primary analysis forest plotIMBRUVICA® (ibrutinib) RESONATE™-2 trial primary analysis forest plot

Abbreviations

1L=first-line, CI=confidence interval, CLL=chronic lymphocytic leukemia, del=deletion, HR=hazard ratio, IGHV=immunoglobulin heavy-chain variable region gene, IRC=independent review committee, iwCLL=International Workshop on Chronic Lymphocytic Leukemia, LTFU=long-term follow-up, 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. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437. 3Data on File ABVRRTI77982 4Burger JA, Barr PM, Robak T, et al. Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Unpublished abstract P670. 5Data on File ABVRRTI6502