Page 185 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

R-CHOP with lenalidomide in MYC+ LBCL
Study overview
This multicenter, phase II study was designed by investigators of HOVON and was approved by the medical ethics committee of the Amsterdam UMC. All patients provided written informed consent.The trial was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. An independent data and safety monitoring board conducted a review during the planned interim analysis.
Endpoints
The primary endpoint of the study was CMR on EOT PET-CT scan as determined by central review plus EOT bone marrow (BM) examination in case of BM localization at diagnosis. In case a BM examination was not repeated at EOT in patients with baseline BM localization and the EOT-PET scan showed no BM uptake localization, the response was classified as CMR (based on recent findings that CMR on PET-CT has a high negative predictive value for BM localization) [23,24]. Secondary endpoints were: OS defined as time from registration to death; DFS defined as time from achievement of first CMR on protocol until relapse or death whichever comes first; EFS defined as the time from registration to lack of CMR on EOT PET-CT, relapse or death; and positive predictive value (PPV) and negative predictive value (NPV) of iPET-CT for EOT result.
Statistical analyses
An optimal Simon two-stage design was used with a response rate of 45% as the null hypothesis, and 60% as the alternative hypothesis. With a statistical significance level of 5% and a power of 80%, the required number of patients was 77, with an interim analysis for futility involving the first 26 included patients. In order to overcome dropouts due to ineligibility, 85 patients were enrolled. All efficacy analyses were restricted to eligible patients, while safety analyses included all enrolled patients. Data cut-off was June 28, 2019. For the clinical protocol, central pathology review, central PET-CT review and additional statistical information, see the Online Supplementary Data.
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