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

Abstract

The utility of PET-CT in distinguishing Richter's transformation versus chronic lymphocytic leukemia progression after ibrutinib and/or idelalisib was assessed in a post-hoc analysis of a phase 2 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, 8 had Richter's transformation, 2 had another malignancy, and 25 had chronic lymphocytic leukemia. A PET-CT maximum standardized uptake value ≥10 had 71% sensitivity and 50% specificity for detecting Richter's transformation (odds ratio, 2.5 [95% CI: .4–15]; p=.318). Response rate to venetoclax was similar for screening maximum standardized uptake value <10 versus ≥10 (65% vs 62%) (n=127 enrolled), though median progression-free survival was longer with <10 (24.7 vs 15.4 months; p=.0335). Six developed Richter’s transformation on venetoclax, of whom 2 had screening biopsy demonstrating chronic lymphocytic leukemia (others did not have biopsy) and 5 had screening maximum standardized uptake value <10. We have defined the test characteristics for PET-CT to distinguish progression of chronic lymphocytic leukemia 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 maximum standardized uptake value ≥10 cutoff. This cutoff did not identify venetoclax-treated patients with an inferior response but may be predictive of inferior progression-free survival. ClinicalTrials.gov; NCT02141282.