78% statistically significant reduction in risk of progression or death1,2
RESONATE™: IMBRUVICA® FOR
RELAPSED/
REFRACTORY CLL/SLL
RESONATE™ Study Design1,2
Phase 3, multicenter, open-label trial of previously treated CLL/SLL (N=391). Patients with del17p were included (n=127). Patients were randomized 1:1 to IMBRUVICA® 420 mg once daily until disease progression or unacceptable toxicity (n=195) or IV ofatumumab for up to 12 doses (n=196). Patients on ofatumumab were able to cross over to IMBRUVICA® upon disease progression. Progression-free survival was the primary endpoint. Overall response rate and overall survival were secondary endpoints.
Primary endpoint: PFS with IMBRUVICA® vs ofatumumab1,2
- Primary analysis with a median IRC-assessed follow-up of 9.4 months2
- Median PFS not reached for IMBRUVICA® vs 8.1 months (95% CI: 7.2, 8.3) with ofatumumab1,2
Long-term follow-up analysis: Investigator-assessed median PFS with an overall follow-up of 63 months1,3
Investigator-assessed long-term follow-up of risk of disease progression or death3
- Median time on study was 56 months (range, 0.1 to 63 months)3
- 44.1 months in the IMBRUVICA® arm (95% CI: 38.5, 56.9)1
- 8.1 months in the ofatumumab arm (95% CI: 7.8, 8.3)1
The timing for long-term follow-up was not prespecified, and the analysis was descriptive in nature.
Ibrutinib was superior to ofatumumab in difficult-to-treat patients with relapsed or refractory CLL or SLL, as measured by progression-free survival, overall survival, and response.”2
— Byrd et al. N Engl J Med. 2014;371(3):213-223.
Addressing the treatment gap in high-risk del17p CLL/SLL
Frequency of del17p increases with line of therapy4-11
Del17p is a strong genetic predictor of poor outcomes4
| Rapid disease progression | Reduced survival |
|---|---|
| Patients with del17p have a median PFS <1 year from diagnosis vs >4 years for all other CLL/SLL patients with normal cytogenetics9 | Patients with del17p have a median OS <3 years from diagnosis vs >9 years for all other CLL/SLL patients with normal cytogenetics9 |
Results from an independent, prospective, single-center, observational analysis of patients with CLL (N=325). The primary endpoint was survival from the time of diagnosis based on mutation status (high-risk cytogenetics included del17p, del11q, or 12q trisomy). Median follow-up was 70 months.9 (Note: This was not an IMBRUVICA® study.)
Prolonged progression-free survival in previously treated patients with del17p1
Primary analysis for del17p subgroup: IRC-assessed PFS with IMBRUVICA® vs ofatumumab with a median follow-up of 9.7 months1,3
75% reduction in risk of disease progression or death1-3
PFS results for IMBRUVICA® (n=63) vs ofatumumab (n=64) in the del17p subset of RESONATE™ patients1
- Median PFS not reached for IMBRUVICA® vs 5.8 months (95% Cl: 5.3, 7.9) with ofatumumab1
Long-term follow-up analysis for del17p subgroup: Investigator-assessed PFS with an overall follow-up of 63 months per iwCLL criteria1-3
Investigator-assessed long-term follow-up of risk of disease progression or death3
Investigator-assessed median PFS in patients with del17p per iwCLL criteria1,3,5,12
- Median time on study was 56 months (range, 0.1 to 63 months)3
- 40.6 months in the IMBRUVICA® arm (95% CI: 25.4, 44.6)1
- 6.2 months in the ofatumumab arm (95% CI: 4.6, 8.1)1
The timing for long-term follow-up was not prespecified, and the analysis was descriptive in nature.
Abbreviations
CI=confidence interval, CLL=chronic lymphocytic leukemia, del=deletion, HR=hazard ratio, IRC=independent review committee, IV=intravenous, iwCLL=International Workshop on Chronic Lymphocytic Leukemia, OS=overall survival, PFS=progression-free survival, SLL=small lymphocytic lymphoma.
References
1. IMBRUVICA® (ibrutinib) Prescribing Information. 2. Byrd JC, Brown JR, O’Brien S, et al. lbrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223. 3. Data on file. Pharmacyclics LLC. 4. Schnaiter A, Stilgenbauer S. 17p deletion in chronic lymphocytic leukemia: risk stratification and therapeutic approach. Hematol Oncol Clin North Am. 2013;27(2):289-301. 5. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute—Working Group 1996 guidelines. Blood. 2008;111(12):5446-5456. 6. Grever MR, Lucas DM, Dewald GW, et al. Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup phase III trial E2997. J Clin Oncol. 2007;25(7):799-804. 7. Stilgenbauer S, Zenz T, Winkler D, et al. Genomic aberrations, VH mutation status and outcome after fludarabine and cyclophosphamide (FC) of FC plus rituximab (FCR) in the CLL8 trial. Presented at: 50th Annual ASH Meeting; December 6-9, 2008; San Francisco, CA. Abstract 781. 8. Stilgenbauer S, Kröber A, Busch R, et al. 17p deletion predicts for inferior overall survival after fludarabine-based first line therapy in chronic lymphocytic leukemia: first analysis of genetics in the CLL4 trial of the GCLLSG. In: Blood (ASH Annual Meeting Abstracts). 2005;106(11):Abstract 715. 9. Döhner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910-1916. 10. Lozanski G, Heerema NA, Flinn IW, et al. Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood. 2004;103(9):3278-3281. 11. Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009;27(24):3994-4001. 12. Hallek M, Cheson BD, Catovsky D, et al. Response assessment in chronic lymphocytic leukemia treated with novel agents causing an increase of peripheral blood lymphocytes (e-Letter). Blood. 2012;119(23):5348.