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

被引：103

作者：

Fraser, G. ^{[1
]}

Cramer, P. ^{[2
,3
]}

Demirkan, F. ^{[4
]}

Silva, R. Santucci ^{[5
]}

Grosicki, S. ^{[6
]}

Pristupa, A. ^{[7
]}

Janssens, A. ^{[8
]}

Mayer, J. ^{[9
]}

Bartlett, N. L. ^{[10
]}

Dilhuydy, M-S ^{[11
]}

Pylypenko, H. ^{[12
]}

Loscertales, J. ^{[13
]}

Avigdor, A. ^{[14
,15
]}

Rule, S. ^{[16
]}

Villa, D. ^{[17
]}

Samoilova, O. ^{[18
]}

Panagiotidis, P. ^{[19
]}

Goy, A. ^{[20
]}

Pavlovsky, M. A. ^{[21
]}

Karlsson, C. ^{[22
,23
]}

Hallek, M. ^{[24
]}

Mahler, M. ^{[25
]}

Salman, M. ^{[25
]}

Sun, S. ^{[25
]}

Phelps, C. ^{[25
]}

Balasubramanian, S. ^{[26
]}

Howes, A. ^{[27
]}

Chanan-Khan, A. ^{[28
]}

机构：

[1] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada

[2] Univ Cologne, Ctr Integrated Oncol, Dept Internal Med, Cologne, Germany

[3] Univ Cologne, German CLL Study Grp, Cologne, Germany

[4] Dokuz Eylul Univ, Div Hematol, Izmir, Turkey

[5] IEP Sao Lucas Hemomed Oncol & Hematol, Sao Paulo, Brazil

[6] Silesian Med Univ, Fac Publ Hlth, Dept Canc Prevent, Katowice, Poland

[7] Reg Clin Hosp, Ryazan, Russia

[8] Univ Ziekenhuizen Leuven, Leuven, Belgium

[9] Masaryk Univ, Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic

[10] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA

[11] Hop Haut Leveque, Bordeaux, France

[12] Cherkassy Reg Oncol Ctr, Dept Hematol, Cherkassy, Ukraine

[13] Hosp Univ La Princesa, Hematol Dept, IIS IP, Madrid, Spain

[14] Chaim Sheba Med Ctr, Div Hematol & Bone Marrow Transplantat, Tel Hashomer, Israel

[15] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[16] Plymouth Univ, Dept Haematol, Med Sch, Plymouth, Devon, England

[17] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC, Canada

[18] Nizhny Novogorod Reg Clin Hosp, Nizhny Novogorod, Nizhnii Novgorod, Russia

[19] Univ Athens, Dept Propedeut Med 1, Athens, Greece

[20] Hackensack Univ Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA

[21] Fundaleu, Dept Hematol, Buenos Aires, DF, Argentina

[22] Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden

[23] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden

[24] Univ Cologne, Dept Internal Med 1, Cologne, Germany

[25] Janssen Res & Dev, Raritan, NJ USA

[26] Janssen Res & Dev, Spring House, PA USA

[27] Janssen Res & Dev, High Wycombe, Bucks, England

[28] Mayo Clin, Canc Ctr, Jacksonville, FL 32224 USA

来源：

LEUKEMIA | 2019年 / 33卷 / 04期

关键词：

KINASE INHIBITOR IBRUTINIB; ATRIAL-FIBRILLATION; RESIDUAL DISEASE; CHEMOIMMUNOTHERAPY; WORKING; CLL;

D O I：

10.1038/s41375-018-0276-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 34) 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.

引用

页码：969 / 980

页数：12

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