Abstract CT132: Long-term treatment with single-agent ibrutinib 420 mg leads to durable responses including complete responses in CLL
Authors: Coutre Steven , Furman Richard , Flinn Ian , Burger Jan , Blum Kristie , Sharman Jeff , Jones Jeffrey , Wierda William , Zhao Weiqiang , Heerema Nyla , Johnson Amy , Tran Anh , Zhou Cathy , Bilotti Elizabeth , James Danelle , Byrd John , O'Brien Susan 
Published: August 2015

Background: Ibrutinib (ibr), a first-in-class, once-daily, oral, covalent inhibitor of Bruton's tyrosine kinase, has single-agent efficacy and acceptable toxicity in treatment-naïve (TN) [Lancet Oncology 2013] and previously-treated chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) patients (pts) [NEJM 2014]. Ibrutinib (Imbruvica®) is indicated for treatment of pts with CLL receiving one prior therapy and for pts with del17p CLL. We present efficacy and safety data with up to 45 months of follow-up for pts receiving ibr at the approved 420 mg dose.

Methods: Analysis included all pts receiving ibr 420 mg/day, dosed until disease progression in the phase I/IIb study PCYC-1102, and the PCYC-1103 extension study. Best overall response rate (ORR), including partial response with lymphocytosis (PR-L) was assessed by investigator using iwCLL criteria. Adverse event (AE) collection focused on ≥grade 3 and serious AEs.

Results: Of 94 CLL/SLL pts (27 TN, 67 relapsed/refractory [R/R]) receiving ibr, median age was 68 years (range, 37-84), with 44 (47%) pts aged ≥70 years. 25 (27%) pts (2 TN, 23 R/R) had del17p and 22 (23%, all R/R) had del11q. R/R pts had a median of 4 (range, 1-12) prior therapies. Best ORR was 91% including 14% complete responses (CR) for all pts (CR 26% TN, 9% R/R). Median DOR and PFS were not reached for all pts. Median time on treatment was 25 mos (range, 0-45) for all pts (30 mos TN, 22 mos R/R). The most common ≥grade 3 AEs reported over this follow-up were hypertension (23%), pneumonia (15%), neutropenia (13%), atrial fibrillation (7%), and diarrhea (7%). 50 (53%) pts (22 [81%] TN, 28 [42%] R/R) remained on treatment for &gt;2 years. At analysis, 22 (81%) TN and 40 (60%) R/R pts continued on ibrutinib. During follow-up, 12 pts discontinued treatment due to disease progression and 12 due to an AE.

Conclusions: Single-agent ibrutinib led to durable responses including 14% CRs in pts with TN or R/R CLL/SLL, with up to 45 months of follow-up.

Efficacy parameterTNR/R(n = 27)(n = 67)ORR23 (85%)63 (94%)CR7 (26%)6 (9%)PR/PR-L16 (59%)57 (85%)DOR, mos (95% Cl)NR (NE, NE)NR (36, NE)30-mo PFS (95% Cl)96% (74, 99)76% (63, 85)30-mo OS rate (95% Cl)96% (78, 99)87% (76, 93)DOR, duration of response; NE, not estimated; NR, not reached; PFS, progression-free survival; OS, overall survival

Citation Format: Steven Coutre, Richard Furman, Ian Flinn, Jan Burger, Kristie Blum, Jeff Sharman, Jeffrey Jones, William Wierda, Weiqiang Zhao, Nyla Heerema, Amy Johnson, Anh Tran, Cathy Zhou, Elizabeth Bilotti, Danelle James, John Byrd, Susan O'Brien. Long-term treatment with single-agent ibrutinib 420 mg leads to durable responses including complete responses in CLL. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT132. doi:10.1158/1538-7445.AM2015-CT132