Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL

Abstract

Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.

Prospective Study of 3′-Deoxy-3′-18F-Fluorothymidine PET for Early Interim Response Assessment in Advanced-Stage B-Cell Lymphoma

“…Time between end of cycle and FLT iPET was 9.8 ± 1.9 days for cohort 1 and 9.4 ±1.2 days for cohort 2. Complete proliferative response (CPR) was observed in 29 patients (grade 1, n= 21; grade 2, n= 7; grade 3, n=1), including three patients without baseline FLT PET: since aggressive lymphoma is FL-avid at baseline (14–16), lack of uptake in residual nodes on iPET was considered CPR. The other 26 patients showed partial response (grade 4, n= 22) or progression (grade 5, n= 4).…”

“…In some studies (14,15) FLT ΔSUV on iPET after one cycle emerged as a predictor of survival, but baseline FLT-SUV did not. An optimal cut-point was not reported.…”

FDG-PET imaging in hematological malignancies

“…FLT-PET may also have potential application in evaluating the addition of novel therapies to current re-induction regimens 137 , as well as identifying future non-responders to R-CHOP treatment among aggressive B-cell NHL's by their high FLT uptake and proliferation rate, enabling a risk-adapted treatment approach in these patients 138 . In two recent studies, higher reduction in FLT uptake on interim FLT-PET was a predictor of improved PFS and OS in patients with aggressive lymphomas 139, 140 . A recent pilot study has demonstrated that FLT uptake in bone marrow may be useful for assessment of treatment response as early as 2 days after chemotherapy initiation in AML patients 141 .…”

Diffuse Large B-Cell Lymphoma: Prospective Multicenter Comparison of Early Interim FLT PET/CT versus FDG PET/CT with IHP, EORTC, Deauville, and PERCIST Criteria for Early Therapeutic Monitoring

“…Baseline FLT uptake has been shown to be a negative predictor of response to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in DLBCL and was significantly correlated with the International Prognostic Index (18). Moreover, preliminary studies have shown that FLT PET allows noninvasive assessment of tumor grading and early response assessment (19)(20)(21)(22)(23)(24).…”