Utility of positron emission tomography-computed tomography in patients with chronic lymphocytic leukemia following B-cell receptor pathway inhibitor therapy

• Published in: Haematologica (Roma) Vol. 104; no. 11; pp. 2258 - 2264
• Main Authors: Mato, Anthony R., Wierda, William G., Davids, Matthew S., Cheson, Bruce D., Coutre, Steven E., Choi, Michael, Furman, Richard R., Heffner, Leonard, Barr, Paul M., Eradat, Herbert, Ford, Sharanya M., Zhou, Lang, Verdugo, Maria, Humerickhouse, Rod A., Potluri, Jalaja, Byrd, John C.
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.11.2019
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2018.207068

The utility of positron emission tomography-computed tomography (PET-CT) in distinguishing Richter's transformation chronic lymphocytic leukemia (CLL) progression after ibrutinib and/or idelalisib was assessed in a 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; =0.318]. Response rate to venetoclax was similar for screening SUVmax <10 ≥10 (65% 62%) (n=127 enrolled), though median progression-free survival was longer at <10 months (24.7 15.4 months; =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 signaling 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 identify venetoclax-treated patients with an inferior response but may be predictive of inferior progression-free survival. (Registered at ).