Citations 12
INTEGRATED ANALYSIS: OUTCOMES OF IBRUTINIB‐TREATED PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LEUKEMIA (CLL/SLL) WITH HIGH‐RISK PROGNOSTIC FACTORS
Fraser, Graeme , Brown, Jennifer R. , Byrd, John C. , Dilhuydy, M.S., Jaeger, Ulrich, Moreno, Carol , Chanan‐Khan, A.A., Mahler, Michelle, Salman, Mariya, Cheng, Minghua , Londhe, Anil, Ninomoto, Joi , Howes, Angela, James, Danelle F. , Kipps, Thomas J. , Coutré, Steven , Barrientos, Jacqueline C. , Barr, Paul M. , O’Brien, Susan , Hillmen, Peter , Cramer, Paula , Stilgenbauer, Stephan , Hallek, Michael
Hematological Oncology | June 7, 2017 | Volume: 35 | Issue: S2 | Pages: 109-111
Ibrutinib combined with bendamustine and rituximab (BR) in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): First results from a randomized, double-blind, placebo-controlled, phase III study.
Chanan‐Khan, Asher , Fraser, Graeme , Silva, Rodrigo Santucci, Pylypenko, Halyna, Janssens, Ann , Pristupa, Alexander , Mayer, Jiřı́ , Dilhuydy, Marie‐Sarah, Loscertales, Javier, Avigdor, Abraham , Rule, Simon , Sun, Steven , Mahler, Michelle, Salman, Mariya, Howes, Angela, Hallek, Michael , Cramer, Paula , Demırkan, Fatih , Grosicki, Sebastian , Bartlett, Nancy L.
Journal of Clinical Oncology | February 24, 2017 | Volume: 33 | Issue: 18_suppl | Pages: LBA7005-LBA7005
10.1200/jco.2015.33.18_suppl.lba7005
LBA7005 Background: The phase III HELIOS study evaluated the first-in-class, oral covalent BTK inhibitor ibrutinib in combination with BR (BR+ibr) vs BR plus placebo (BR+plb) in patients (pts) with previously treated CLL/SLL. The preplanned interim analysis reported here showed that the primary end point was met, upon which the IDMC recommended unblinding the study. Methods: Pts received BR ( ≤ 6 cycles) and were randomized 1:1 to ibr (420 mg daily) or plb. Purine analog refractoriness was a stratification factor. Pts with del17p ( > 20% of cells) were excluded. Primary end point was independent review committee (IRC)-assessed progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR) per IRC. Results: 578 pts were randomized (289 per arm); median age 64 yrs; 38% Rai Stage III/IV; median 2 prior therapies. 6 cycles of BR were completed in 83% and 78% of pts in the ibr and plb arms, respectively. At a median follow-up of 17.2 months, IRC-assessed PFS was significantly longer with BR+ibr vs BR+plb (median not reached vs 13.3 months; HR: 0.203, 95% CI: 0.150-0.276, P< 0.0001); PFS results were consistent across high-risk subgroups. ORR and CR/CRi rates were 82.7% vs 67.8% (P< 0.0001) and 10.4% vs 2.8%. Median OS was not reached. 90 pts (31%) in the BR+plb arm with confirmed PD crossed over to receive ibr, as permitted per the protocol. Incidence of most AEs was similar between arms. The most common all-grade AEs with BR+ibr and BR+plb were neutropenia (58.2% vs 54.7%) and nausea (36.9% vs 35.2%); most common grade 3/4 AEs were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15.0% each arm). Rates of grade 3/4 atrial fibrillation were 2.8% and 0.7%, and major hemorrhage were 2.1% and 1.7%. Fatigue (FACIT-Fatigue) was improved with BR+ibr vs BR+plb. Conclusions: The addition of ibr to BR reduced the risk of progression or death by 80% compared with BR+plb. ORR was also significantly improved. Safety of BR+ibr was consistent with the known profiles for BR and ibr. The data further support ibr as an important treatment option for pts with previously treated CLL/SLL. Clinical trial information: EudraCT No. 2012-000600-15; UTN No. U1111-1135-3745.