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A.R. Mato et al.
occurrence of RT in the current study suggests that most patients with RT were prospectively identified and excluded from participating in this study utilizing the pre- specified criteria for biopsy based on PET-CT imaging and other clinical features. It is also possible that there was a treatment effect of venetoclax, which would be consistent with the results for the DLBCL patients with RT in a pre- vious Phase I study across non-Hodgkin lymphomas.24 Venetoclax is currently being studied in CLL patients with RT (clinicaltrials.gov identifier: 03054896).
The primary role of PET-CT in patients with CLL is to identify the most appropriate target for biopsy to assess for the presence of RT or other malignancy. Overall, our data suggest that CLL progression may be more metabol- ically active on PET-CT following BCRi failure as com- pared to chemoimmunotherapy. PET-CT SUVmax cutoff of 10 was able to distinguish suspected RT from CLL pro- gression at screening with a sensitivity of 71% and speci- ficity of 50%, test characteristics which are modest com- pared to those reported in prior studies with chemothera- py or CIT-treated patients.10 SUVmax cutoff of 10 at base- line also did not predict the development of RT in patients on venetoclax. Clinical features, including elevated β-2 microglobulin and LDH may provide additional informa- tion when considering biopsy to confirm RT. Future analyses including assessment of additional genetic fac-
tors, BCR stereotypes, or gene expression could be tested as predictors for the risk of RT following BCRi exposure.
Acknowledgments
Special thanks to the patients and their families, study coordi- nators, and support staff.
Funding
AbbVie and Genentech provided financial support for the study. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g. protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unli- censed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. Data requests can be submitted at any time and the data will be acces- sible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the follow- ing link: https://www.abbvie.com/our-science/clinical-trials/clini- cal-trials-data-and-information-sharing/data-and-information- sharing-with-qualified-researchers.html.
Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol. 2017;19(1):65-
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