Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients

Abstract

Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was >80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies.

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

“…There are no studies that looked at the predictive value of I-PET in MYC-DLBCL patients only. But these results are in line with previous studies, where MYC status was not assessed [7,8,19,20]. In our study, 28.8% of the MYC + patients had positive I-PET scans.…”

“…In our study, 28.8% of the MYC + patients had positive I-PET scans. This PET-positivity rate was comparable with the PET-positivity rate of MYC - patients (23.8%), and with PET-positivity rates reported in a recent individual patient data analysis [ 8 ]. However, Dunleavy and colleagues reported that 70.8% of MYC + DLBCL patients treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) were PET positive after two cycles of treatment [ 18 ].…”

“…Secondly, the timing of I-PET differed between subgroups. A recent individual patient data analysis showed that I-PET positivity using DS criteria at I-PET3 and I-PET4 was almost identical (21.7 vs 21.2%) [ 8 ], implying that the I-PET-positivity rate for MYC - DLBCL patients would be similar after three cycles of treatment. However, a small effect of timing cannot be precluded in our results.…”

“…To improve consistency of visual assessment, quantitative cut-offs were suggested based on the maximum hepatic standardized uptake value (SUV max ) [ 6 ]. In non-selected DLBCL patients, a negative I-PET has a high negative predictive value (NPV) for outcome, but the positive predictive value (PPV) is limited [ 7 , 8 ]. One small study that included 28 MYC + DLBCL patients reported lower NPV values compared to non-selected DLBCL patients [ 9 ].…”

Vital Hepatic Lymphoma Residuum or Excessive Immune Response? Challenging Treatment Decisions in a Patient With Systemic Lupus Erythematosus and Liver-Dominant Diffuse Large B-Cell Lymphoma: Case Report

“…Standard first-line immunochemotherapy consists of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). About two-thirds of DLBCL patients achieve long-term disease-free survival by R-CHOP, whereas the other one-third have a poor prognosis and low response rates to salvage treatment ( 7 ).…”