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      Complex Karyotype is a Stronger Predictor than Del(17p) for Inferior Outcome in Relapsed or Refractory CLL Patients Treated with Ibrutinib-Based Regimens

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          Abstract

          Background

          Ibrutinib is active in patients with relapsed/refractory (R/R) CLL. In patients treated with ibrutinib for R/R CLL, del(17p) identified by interphase fluorescence in situ hybridization (FISH) is associated with inferior progression-free survival, despite equivalent initial response rates. Del(17p) is frequently associated with complex metaphase karyotype (CKT); the prognostic significance of CKT in ibrutinib-treated patients has not been reported.

          Methods

          We reviewed 88 patients treated for R/R CLL at MD Anderson Cancer Center with investigational ibrutinib-based regimens from 2010–2013. Pre-treatment FISH and Lipopolysaccharide-stimulated metaphase cytogenetic analysis were performed on bone marrow.

          Results

          Adequate pre-treatment metaphase karyotype was available for 56/88 patients. Karyotype was complex in 21 of 56 cases; 17 of the 21 had del(17p) by FISH. Overall response rate, including partial remission with persistent lymphocytosis, was 94% with 17% complete responses. In multivariable analysis (MVA), only CKT was significantly associated with event-free survival (EFS) [HR 6.6 (1.7–25.6), p=0.006]. Fludarabine-refractory CLL [HR 6.9 (1.8–27.1), p=0.005] and CKT [HR 5.9 (1.6–22.2), p=0.008] were independently associated with inferior overall survival (OS) in MVA. Del(17p) by FISH was not significantly associated with EFS or OS in MVA.

          Conclusions

          CKT is a powerful predictor of outcome in ibrutinib-treated patients with R/R CLL and may be a stronger predictor of biological behavior than del(17p) by FISH. Given their relatively poor outcomes, patients with CKT are ideal candidates for studies of consolidative treatment strategies or novel treatment combinations.

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          Author and article information

          Journal
          0374236
          2771
          Cancer
          Cancer
          Cancer
          0008-543X
          1097-0142
          26 April 2016
          20 July 2015
          15 October 2015
          15 October 2016
          : 121
          : 20
          : 3612-3621
          Affiliations
          [1 ]Department of Leukemia, UT MD Anderson Cancer Center, Houston TX 77030 USA
          [2 ]Department of Biostatistics, UT MD Anderson Cancer Center, Houston TX 77030 USA
          Author notes
          Correspondence to: Michael J. Keating, MBBS, Professor of Medicine, Department of Leukemia, 1515 Holcombe Blvd, Unit 428, Houston, Texas 77030, (713) 745-2376 (phone), (713) 794-1602 (fax), mkeating@ 123456mdanderson.org
          Article
          PMC4866653 PMC4866653 4866653 nihpa773424
          10.1002/cncr.29566
          4866653
          26193999
          96a41838-0689-4785-be3a-4702985e1ed7
          History
          Categories
          Article

          ibrutinib,CLL,complex karyotype,del(17p),relapsed and refractory

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