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

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. KarlssonM. Hallek, M. Mahler, M. Salman, S. Sun, C. Phelps, S. Balasubramanian, A. Howes, Asher A Chanan Khan

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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.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - Jan 1 2018

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B-Cell Chronic Lymphocytic Leukemia
Placebos
Disease-Free Survival
PCI 32765
Bendamustine Hydrochloride
Rituximab
Survival
Residual Neoplasm
Advisory Committees
Survival Rate
Research Personnel
Incidence

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. / Fraser, G.; Cramer, P.; Demirkan, F.; Silva, R. Santucci; Grosicki, S.; Pristupa, A.; Janssens, A.; Mayer, J.; Bartlett, N. L.; Dilhuydy, M. S.; Pylypenko, H.; Loscertales, J.; Avigdor, A.; Rule, S.; Villa, D.; Samoilova, O.; Panagiotidis, P.; Goy, A.; Pavlovsky, M. A.; Karlsson, C.; Hallek, M.; Mahler, M.; Salman, M.; Sun, S.; Phelps, C.; Balasubramanian, S.; Howes, A.; Chanan Khan, Asher A.

In: Leukemia, 01.01.2018.

Research output: Contribution to journalArticle

Fraser, G, Cramer, P, Demirkan, F, Silva, RS, Grosicki, S, Pristupa, A, Janssens, A, Mayer, J, Bartlett, NL, Dilhuydy, MS, Pylypenko, H, Loscertales, J, Avigdor, A, Rule, S, Villa, D, Samoilova, O, Panagiotidis, P, Goy, A, Pavlovsky, MA, Karlsson, C, Hallek, M, Mahler, M, Salman, M, Sun, S, Phelps, C, Balasubramanian, S, Howes, A & Chanan Khan, AA 2018, 'Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma', Leukemia. https://doi.org/10.1038/s41375-018-0276-9
Fraser, G. ; Cramer, P. ; Demirkan, F. ; Silva, R. Santucci ; Grosicki, S. ; Pristupa, A. ; Janssens, A. ; Mayer, J. ; Bartlett, N. L. ; Dilhuydy, M. S. ; Pylypenko, H. ; Loscertales, J. ; Avigdor, A. ; Rule, S. ; Villa, D. ; Samoilova, O. ; Panagiotidis, P. ; Goy, A. ; Pavlovsky, M. A. ; Karlsson, C. ; Hallek, M. ; Mahler, M. ; Salman, M. ; Sun, S. ; Phelps, C. ; Balasubramanian, S. ; Howes, A. ; Chanan Khan, Asher A. / Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. In: Leukemia. 2018.
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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.",
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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, Asher A

PY - 2018/1/1

Y1 - 2018/1/1

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.

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