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

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 idelalisib 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 survival 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 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 clinicaltrials.gov identifier: 02141282).

Figure 1.

Outcomes on venetoclax stratified by screening maximum standardized uptake value of 18-F-fluorodeoxyglucose (SUVmax) by positron emission tomography-computed tomography imaging. Shown are the investigator-assessed (A) progression-free survival (PFS), and (B) overall survival (OS) on venetoclax as assessed by the investigator for patients with screening SUVmax <10 (n=114) and SUVmax ≥10 (n=13). (C) Investigator-assessed duration of response is shown for responders on venetoclax stratified by screening SUVmax <10 (n=74) and SUVmax ≥10 (n=8). Number of patients at risk for the event at each time point is shown below each curve. Tick marks represent censored data. n: number.

Figure 2.

Time to chronic lymphocytic leukemia (CLL) progression or Richter’s transformation (RT) on venetoclax. Shown is the cumulative incidence of CLL progression or Richter’s transformation on venetoclax. Thirty-three patients discontinued venetoclax due to CLL progression and six due to biopsy-confirmed RT following both imaging and clinical changes. Median time to CLL progression was 8.5 months (range: 0.1-28 months) and to RT was 12.8 months (range: 4.4–19.7 months). Tick marks represent patients with events.