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Clin Lymphoma Myeloma Leuk. 2018 Feb;18(2):114-124.e2. doi: 10.1016/j.clml.2017.11.010. Epub 2017 Dec 6.

Prognostic Testing Patterns and Outcomes of Chronic Lymphocytic Leukemia Patients Stratified by Fluorescence In Situ Hybridization/Cytogenetics: A Real-world Clinical Experience in the Connect CLL Registry.

Author information

1
Center for CLL, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA. Electronic address: Anthony.Mato@uphs.upenn.edu.
2
Cardinal Health, Dublin, OH.
3
Division of Hematology, Mayo Clinic, Rochester, MN.
4
Division of Hematology and Oncology, Department of Medicine, New York-Presbyterian/Columbia University Medical Center, New York, NY.
5
Moores Cancer Center, UC San Diego Health, La Jolla, CA.
6
NorthShore University HealthSystem, Evanston, IL.
7
Emory University, Atlanta, GA.
8
Summit Medical Group, MD Anderson Cancer Center, Morristown, NJ.
9
Dana-Farber Cancer Institute, Boston, MA.
10
Celgene Corporation, Summit, NJ.
11
Celgene Corporation, Overland Park, KS.
12
Celgene Corporation, San Francisco, CA.
13
Willamette Valley Cancer Institute, US Oncology, Springfield, OR.

Abstract

INTRODUCTION:

Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy.

PATIENTS AND METHODS:

In the present analysis of the Connect CLL Registry (ClinicalTrials.gov identifier, NCT01081015), a prospective observational cohort study of patients treated across 199 centers, the patterns of prognostic testing and outcomes of patients with unfavorable-risk genetics were analyzed. From 2010 to 2014, 1494 treated patients were enrolled in the registry by line of therapy (LOT), and stratified by the results of cytogenetic/fluorescence in situ hybridization (FISH) testing into 3 risk levels: unfavorable (presence of del[17p] or del[11q]), favorable (absence of del[17p] and del[11q]), and unknown.

RESULTS:

Cytogenetic/FISH testing was performed in 861 patients (58%) at enrollment; only 40% of these patients were retested before starting a subsequent LOT. Of those enrolled at the first LOT, unfavorable-risk patients had inferior event-free survival compared with favorable-risk patients (hazard ratio, 1.60; P = .001). Event-free survival was inferior with bendamustine-containing regimens (P < .0001). Event-free survival did not differ significantly between risk groups for patients treated with ibrutinib or idelalisib in the relapse/refractory setting. The predictors of reduced event-free survival included unfavorable-risk genetics, age ≥ 75 years, race, and treatment choice at enrollment.

CONCLUSION:

The present study has shown that prognostic cytogenetic/FISH testing is infrequently performed and that patients with unfavorable-risk genetics treated with immunochemotherapy combinations have worse outcomes. This underscores the importance of performing prognostic genetic testing for all CLL patients to guide treatment.

KEYWORDS:

Community setting; Cytogenetic testing; Kinase inhibitor; Prognosis; Unfavorable risk

PMID:
29352719
DOI:
10.1016/j.clml.2017.11.010
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