TY - JOUR
T1 - Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma
AU - Fraser, G.
AU - Cramer, P.
AU - Demirkan, F.
AU - Silva, R. Santucci
AU - Grosicki, S.
AU - Pristupa, A.
AU - Janssens, A.
AU - Mayer, J.
AU - Bartlett, N. L.
AU - Dilhuydy, M. S.
AU - Pylypenko, H.
AU - Loscertales, J.
AU - Avigdor, A.
AU - Rule, S.
AU - Villa, D.
AU - Samoilova, O.
AU - Panagiotidis, P.
AU - Goy, A.
AU - Pavlovsky, M. A.
AU - Karlsson, C.
AU - Hallek, M.
AU - Mahler, M.
AU - Salman, M.
AU - Sun, S.
AU - Phelps, C.
AU - Balasubramanian, S.
AU - Howes, A.
AU - Chanan-Khan, A.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85054727985
U2 - 10.1038/s41375-018-0276-9
DO - 10.1038/s41375-018-0276-9
M3 - Article
C2 - 30315239
AN - SCOPUS:85054727985
SN - 0887-6924
VL - 33
SP - 969
EP - 980
JO - Leukemia
JF - Leukemia
IS - 4
ER -