Page 152 - 2019_11 Resto del Mondo-web
P. 152

Ferrata Storti Foundation
Haematologica 2019 Volume 104(11):2258-2264
Chronic Lymphocytic Leukemia
Utility of positron emission tomography-computed tomography in patients with chronic lymphocytic leukemia following B-cell receptor pathway inhibitor therapy
Anthony R. Mato,1 William G. Wierda,2 Matthew S. Davids,3 Bruce D. Cheson,4 Steven E. Coutre,5 Michael Choi,6 Richard R. Furman,7 Leonard Heffner,8
Paul M. Barr,9 Herbert Eradat,10 Sharanya M. Ford,11 Lang Zhou,11
Maria Verdugo,11 Rod A. Humerickhouse,11 Jalaja Potluri11 and John C. Byrd12
1
CLL Program, Leukemia Service, Division of Hematologic Oncology, Memorial Sloan Kettering
Cancer Center, New York, NY; 2University of Texas MD Anderson Cancer Center, Houston, TX; 3Dana-Farber Cancer Institute, Boston, MA; 4Georgetown University Hospital, Washington, DC; 5Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA; 6UCSD Moores Cancer Center, San Diego, CA; 7Weill Cornell Medicine, New York, NY; 8Emory University School of Medicine, Atlanta, GA; 9Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY; 10University of California Los Angeles, Los Angeles, CA; 11AbbVie Inc. North Chicago, IL and 12The Ohio State University, Columbus, OH, USA
ABSTRACT
The utility of positron emission tomography-computed tomography (PET-CT) in distinguishing Richter’s transformation versus chronic lymphocytic leukemia (CLL) progression after ibrutinib and/or idelal- isib was assessed in a post hoc analysis of a phase II study of venetoclax. Patients underwent PET-CT at screening and were not enrolled/treated if Richter’s transformation was confirmed pathologically. Of 167 patients screened, 57 met criteria for biopsy after PET-CT. Of 35 patients who underwent biopsy, eight had Richter’s transformation, two had another malignancy, and 25 had CLL. A PET-CT maximum standardized uptake value (SUVmax) ≥10 had 71% sensitivity and 50% specificity for detecting Richter’s transformation [Odds Ratio (OR): 2.5, 95%CI: 0.4-15; P=0.318]. Response rate to venetoclax was similar for screening SUVmax <10 versus ≥10 (65% vs. 62%) (n=127 enrolled), though median progression-free sur- vival was longer at <10 months (24.7 vs. 15.4 months; P=0.0335). Six patients developed Richter’s transformation on venetoclax, of whom two had screening biopsy demonstrating CLL (others did not have a biopsy) and five had screening SUVmax <10. We have defined the test characteristics for PET-CT to distinguish progression of CLL as compared to Richter’s transformation when biopsied in patients treated with B-cell receptor sig- naling pathway inhibitors. Overall diminished sensitivity and specificity as compared to prior reports of patients treated with chemotherapy/ chemoimmunotherapy suggest it has diminished ability to discriminate these two diagnoses using a SUVmax ≥10 cutoff. This cutoff did not iden- tify venetoclax-treated patients with an inferior response but may be pre- dictive of inferior progression-free survival. (Registered at clinicaltrials.gov identifier: 02141282)
Introduction
Chronic lymphocytic leukemia (CLL) is an indolent, low-grade B-cell lymphopro- liferative disorder, which can undergo Richter’s transformation (RT) to a diffuse large B-cell lymphoma (DLBCL)1 or Hodgkin lymphoma. The prognosis of RT is extremely poor, with a median survival of about eight months.2-5 Clinical signs and symptoms associated with RT are non-specific and include rapid clinical deteriora- tion.6 Potential factors that may predict RT include mutational status, such as TP53
Correspondence:
ANTHONY R. MATO
matoa@mskcc.org
Received: September 28, 2018. Accepted: March 20, 2019. Pre-published: March 28, 2019.
doi:10.3324/haematol.2018.207068
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/11/2258
©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
2258
haematologica | 2019; 104(11)
ARTICLE


































































































   150   151   152   153   154