Long-Term Studies Assessing Outcomes of Ibrutinib Therapy in Patients With Del(11q) Chronic Lymphocytic Leukemia

被引：39

作者：

Kipps, Thomas J. ^{[1
]}

Fraser, Graeme ^{[2
]}

Coutre, Steven E. ^{[3
]}

Brown, Jennifer R. ^{[4
]}

Barrientos, Jacqueline C. ^{[5
]}

Barr, Paul M. ^{[6
]}

Byrd, John C. ^{[7
]}

O'Brien, Susan M. ^{[8
]}

Dilhuydy, Marie-Sarah ^{[9
]}

Hillmen, Peter ^{[10
]}

Jaeger, Ulrich ^{[11
]}

Moreno, Carol ^{[12
]}

Cramer, Paula ^{[13
,14
]}

Stilgenbauer, Stephan ^{[15
]}

Chanan-Khan, Asher A. ^{[16
]}

Mahler, Michelle ^{[17
]}

Salman, Mariya ^{[17
]}

Eckert, Karl ^{[18
]}

Solman, Isabelle G. ^{[18
]}

Balasubramanian, Sriram ^{[17
]}

Cheng, Mei ^{[18
]}

Londhe, Anil ^{[17
]}

Ninomoto, Joi ^{[18
]}

Howes, Angela ^{[17
]}

James, Danelle F. ^{[18
]}

Hallek, Michael ^{[13
,14
]}

机构：

[1] UC San Diego Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA

[2] McMaster Univ, Juravinski Canc Ctr, Dept Oncol, Hamilton, ON, Canada

[3] Stanford Univ, Stanford Canc Ctr, Div Hematol, Sch Med, Stanford, CA 94305 USA

[4] Dana Farber Canc Inst, Ctr Chron Lymphocyt Leukemia, Boston, MA 02115 USA

[5] Northwell Hlth Canc Inst, CLL Res & Treatment Program, Hempstead, NY USA

[6] Univ Rochester, Rochester, NY USA

[7] Ohio State Univ, Dept Internal Med, Comprehens Canc Ctr, Div Hematol, Columbus, OH 43210 USA

[8] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA

[9] Hop Haut Leveque, Pessac, France

[10] Univ Leeds, Leeds, W Yorkshire, England

[11] Med Univ Vienna, Div Hematol & Hemostaseol, Vienna, Austria

[12] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[13] Univ Cologne, Dept Internal Med, Cologne, Germany

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

[15] Univ Ulm, Dept Internal Med 3, Ulm, Germany

[16] Mayo Clin, Canc Ctr, Div Hematol, Jacksonville, FL 32224 USA

[17] Janssen Res & Dev, Horsham, PA USA

[18] Pharmacycl LLC, Sunnyvale, CA USA

来源：

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA | 2019年 / 19卷 / 11期

关键词：

Prognostic factors; Risk factors; Small lymphocytic lymphoma; Survival; IN-SITU HYBRIDIZATION; GENOMIC ABERRATIONS; 1ST-LINE TREATMENT; COMPLEX KARYOTYPE; INITIAL THERAPY; OPEN-LABEL; FOLLOW-UP; RITUXIMAB; CLL; CHEMOIMMUNOTHERAPY;

D O I：

10.1016/j.clml.2019.07.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A pooled analysis of 1238 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma from three phase 3 studies found that genomic risk factors were not associated with shorter progression-free survival (PFS) or overall survival for patients treated with ibrutinib. Ibrutinib-treated patients with del(11q) were found to have a longer PFS than those without del(11q). These results suggest less prognostic relevance for certain genomic risk factors with ibrutinib treatment. Background: Certain genomic features, such as del(11q), expression of unmutated immunoglobulin heavy-chain variable region (IGHV) gene, or complex karyotype, predict poorer outcomes to chemotherapy in patients with chronic lymphocytic leukemia (CLL). Patients and Methods: We examined the pooled long-term follow-up data from PCYC-1115 (RESONATE-2), PCYC-1112 (RESONATE), and CLL3001 (HELIOS), comprising a total of 1238 subjects, to determine the prognostic significance of these markers in patients treated with ibrutinib. Results: With a median follow-up of 47 months, ibrutinib-treated patients had longer progression-free survival (PFS) than patients treated in the comparator arm, regardless of genomic risk factors. Among patients treated with ibrutinib, we found that high-risk genomic features were not associated with shorter PFS (63-75% across all subgroups at 42 months) or overall survival (79-83% across all subgroups at 42 months). Surprisingly, we observed that ibrutinib-treated patients with del(11q) actually had a significantly longer PFS than ibrutinib-treated patients without del(11q) (42-month PFS rate 70% vs. 65%, P = .02). Conclusion: These analyses not only demonstrate that genomic risk factors previously associated with poor outcomes lose their adverse prognostic significance but also that del(11q) can be associated with a superior PFS with ibrutinib therapy.

引用

页码：715 / +

页数：14

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