Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

Abstract

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

• Authors: G Fraser, P Cramer, F Demirkan, R Santucci Silva, S Grosicki, A Pristupa, A Janssens, J Mayer, N L Bartlett, M-S Dilhuydy, H Pylypenko, J Loscertales, A Avigdor, S Rule, D Villa, O Samoilova, P Panagiotidis, A Goy, M A Pavlovsky, C Karlsson, M Hallek, M Mahler, M Salman, S Sun, C Phelps, S Balasubramanian, A Howes, A Chanan-Khan
• Journal: Leukemia (Leukemia) Vol. 33 Issue 4 Pg. 969-980 (04 2019) ISSN: 1476-5551 [Electronic] England
• PMID: 30315239 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Piperidines
• Pyrazoles
• Pyrimidines
• ibrutinib
• Rituximab
• Bendamustine Hydrochloride
• Adenine

Topics

• Adenine (analogs & derivatives)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bendamustine Hydrochloride (administration & dosage)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, pathology)
• Male
• Middle Aged
• Piperidines
• Prognosis
• Pyrazoles (administration & dosage)
• Pyrimidines (administration & dosage)
• Rituximab (administration & dosage)
• Survival Rate
• Young Adult