Final 5-year findings from the phase 3 HELIOS study of ibrutinib plus bendamustine and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

Abstract

We report final analysis outcomes from the phase 3 HELIOS study (NCT01611090). Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma without deletion 17p (n = 578) were randomized 1:1 to 420 mg daily ibrutinib or placebo plus ≤6 cycles of bendamustine plus rituximab (BR), followed by ibrutinib or placebo alone. Median follow-up was 63.7 months. Median investigator-assessed progression-free survival was longer with ibrutinib plus BR (65.1 months) than placebo plus BR (14.3 months; hazard ratio [HR] 0.229 [95% confidence interval (CI) 0.183–0.286]; p < .0001). Despite crossover of 63.3% of patients from the placebo plus BR arm to ibrutinib treatment upon disease progression, ibrutinib plus BR versus placebo plus BR demonstrated an overall survival benefit (HR 0.611 [95% CI 0.455–0.822]; p = .0010; median not reached in either arm). Long-term follow-up data confirm the survival benefit of ibrutinib plus BR over BR alone. Safety profiles were consistent with those known for ibrutinib and BR.

Keywords:

• Ibrutinib
• HELIOS phase 3 trial
• 5-year follow-up
• overall survival
• relapsed chronic lymphocytic leukemia

Acknowledgments

Writing assistance was provided by Sally Hassan, PhD, CMPP of Parexel and funded by Janssen Global Services, LLC. The authors would like to thank patients who participated in this trial, their families, investigators, study coordinators, study teams, and nurses.

Disclosure statement

GAMF had a consultant/advisory role with AbbVie and Janssen. FD had a consultant/advisory role with AbbVie and Roche, received research funding from AbbVie and Janssen, honoraria from Amgen and Janssen, and was on a speakers’ bureau for Amgen and Janssen. RSS had a consultant/advisory role with AstraZeneca and Janssen and was on a speakers’ bureau for Janssen. AJ had a consultant/advisory role with Gilead Sciences, Janssen, Roche, and Sanofi Genzyme, was on a speakers’ bureau for AbbVie, Amgen, and Novartis, and received other financial/material support from Celgene. JM received research funding from Janssen-Cilag. NLB had a consultant/advisory role with ADC Therapeutics, Acerta, and BTG Therapeutics and received research funding from Autolus, Bristol Meyers Squibb, Celgene, Forty Seven, Genentech, Immune Design, Janssen, Kite Pharma, Merck, Millennium, Pharmacyclics, and Seattle Genetics. M-SD had a consultant/advisory role with AbbVie and Janssen and received honoraria from AbbVie and Janssen. JL had a consultant/advisory role with AbbVie, AstraZeneca, Gilead Sciences, Janssen, and Roche. SR had a consultant/advisory role with AstraZeneca, BeiGene, Celgene, Celltrion, Gilead Sciences, Janssen, Kite Pharma, Roche, and Sunesis Pharmaceuticals, received research funding from Janssen and Pharmacyclics, and was on a speakers’ bureau for Janssen and Roche. MAP had a consultant/advisory role with AstraZeneca and Janssen, and was on a speakers’ bureau for AbbVie, Janssen, Novartis, and Roche. AG had a consultant/advisory role with and received honoraria from Acerta, Celgene, Gilead Sciences/Kite Pharma, and Janssen, received research funding from Acerta, AstraZeneca, Bayer, CALBG, Celgene, Genentech, Hoffman-La Roche, Janssen, Kite Pharma, MD Anderson, MorphoSys AG, Pharmacyclics, and the University of Nebraska, and is on the board and a shareholder of COTA. AM had a consultant role with and received research funding from AbbVie, Acerta, Janssen, Loxo Oncology, Pharmacyclics, Genentech, Sunesis Pharmaceuticals, and TG Therapeutics, received research funding from DTRM and Regeneron, and was on the Data and Safety Monitoring Board for Celgene and TG Therapeutics. MH had a consultant/advisory role with AbbVie, Celgene, Gilead Sciences, Janssen, Mundipharma, Pharmacyclics, and Roche, received research funding from AbbVie, Celgene, Gilead Sciences, Janssen, Mundipharma, Pharmacyclics, and Roche, and was on a speakers’ bureau for AbbVie, Celgene, Gilead Sciences, Janssen, Mundipharma, Pharmacyclics, and Roche. MS, AC, KN, SB, and AH hold J&J stock and are employed by Janssen R&D. SB also holds AbbVie stock. MT and SS are also employees of Janssen. NS holds J&J stock and is employed by Janssen-Cilag. PC had a consultant/advisory role with AbbVie, Acerta Pharma, AstraZeneca, Janssen-Cilag, and Novartis, was on a speakers’ bureau for AbbVie, F. Hoffmann-LaRoche, and Janssen-Cilag, and received other financial/material support from AbbVie, Acerta Pharma, AstraZenca, F. Hoffmann-LaRoche, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, and Novartis. AC-K, SG, AA, and OS have no conflicts of interest to disclose.

Data availability

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for study data access can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.