Utility of PET-CT in patients with chronic lymphocytic leukemia following B-cell receptor pathway inhibitor therapy.
Mato AR, Wierda WG, Davids MS, Cheson BD, Coutre SE, Choi M, Furman RR, Heffner L, Barr PM, Eradat H, Ford SM, Zhou L, Verdugo M, Humerickhouse RA, Potluri J, Byrd JC
Haematologica in press 03/28/2019
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.