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Letters to the Editor
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Figure 1. SUVmax on a PET scan. (A) Distribution of SUVmax by pathology. (B) Sensitivity, specificity, and positive and negative predictive values of different SUVmax thresholds in detecting Richter transformation (n=54): ©ROC analysis of SUVmax cut-off for identifying Richter transformation. SUV: standardized uptake value; PET: positron emission tomography.
sitivity (91%) and specificity (95%) using a cut-off of SUVmax ≥10.
B-cell receptor pathway inhibitors (BCRi) such as Bruton tyrosine kinase (BTK) inhibitor ibrutinib and phosphatidylinositol 3-kinase (PI3K) inhibitor idelalisib have significantly improved the outcome of CLL. However, CLL patients who progress through BCRi often develop clinically aggressive disease.9-12 Recently Mato et al.12 reported that in CLL patients who progressed on a BCRi therapy and were screened for participation in a clinical trial of venetoclax, SUVmax ≥10 on PET scan had a low sensitivity (71%) and specificity (50%) in detecting RT. However, this study included only eight patients with RT. Given the increasing use of BCRi in clinical prac- tice and the importance of differentiating between RT and progressive CLL, we conducted a single-institution study to further evaluate the diagnostic role of PET scan in CLL patients receiving BCRi therapy with suspected disease progression.
CLL patients on a BCRi treatment who underwent a PET scan for evaluation of potential disease progression between November 2012 and March 2019 were identi- fied from the Mayo Clinic CLL Database.13 CLL patients with no clinical suspicion of disease progression who underwent a PET scan for restaging (i.e., evaluation of treatment response) were excluded. Patients with known
RT or a second malignancy who underwent a PET scan for initial staging or restaging were also excluded. PET images were centrally reviewed by a nuclear radiologist (MSB). Pathology slides in a subset of patients were inde- pendently reviewed by a hematopathologist (MS) for ver- ification.
Between November 2012 and March 2019, 92 CLL patients, who were on a BCRi (ibrutinib [n=90] or idelal- isib [n=2]) and underwent a PET scan to evaluate for potential disease progression, were identified (Table 1). The median age at BCRi initiation was 68 years (range: 43-89), and 69 (75%) were male. Sixty (80%) patients had unmutated immunoglobulin heavy-chain variable region (IGHV). The CLL fluorescence in situ hybridization (FISH) panel showed del(17p) in 19 (28%) and del(11q) in 16 (23%) patients. The median time from BCRi initiation to PET scan was 14 months (range: 0.3-62 months). The median SUVmax was 7.0 (range: 1.1-27.3). The number of patients with a SUVmax of <5 was 33 (36%), ≥5 but <10 was 34 (37%), and ≥10 was 25 (27%). After the PET scan, 38 patients did not undergo tissue biopsy; among those, 34 were treated as persistent CLL (median SUVmax 3.6 [range: 1.1-10.3]), two were treated as presumed RT (SUVmax 19.5 and 27.3, respectively), and two died before a biopsy could be performed (SUVmax 7.8 and 13.5, respec- tively). There were no differences in baseline characteris-
haematologica | 2020; 105(11)