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Purpose MYC  gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[ 18 F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in  MYC  + and  MYC - DLBCL patients. Methods Interim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81  MYC  + and 129  MYC - DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival. Results MYC  + DLBCL patients had significantly more positive EoT-PET scans than  MYC - patients (32.5 vs 15.7%,  p  = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In  MYC  + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the  MYC - patients ( p  = 0.002). Nine (34.6%)  MYC  + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%)  MYC - patient. A total of 80.8% of EoT-PET positive  MYC  + patients showed both increased lesional SUV and MTV compared to I-PET. In  MYC-  patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both  MYC  subgroups (81.8–94.1%). PPV was highest at EoT-PET for  MYC  + patients (61.5%). Conclusion MYC  + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved. Trial registration number and date of registration HOVON-84: EudraCT: 2006–005,174-42, retrospectively registered 01–08-2008. HOVON-130: EudraCT: 2014–002,654-39, registered 26–01-2015

Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements