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.

Graphical abstract

Figure 1.

CONSORT diagram of patient inclusion.

Figure 2.

PPS from day of baseline scan for individual studies included in our analysis. (A) Kaplan-Meier survival curve for 5-year PFS for all studies. (B) Uncorrected Cox regression 2-year PFS for all studies. (C) Cox regression corrected for IPI score for 2-year PFS for all individual studies.

Figure 3.

Two-year PFS Cox regression stratified for DS4-5 I-PET–positive patients and timing. Corrected for low-risk (A), low-intermediate risk (B), high-intermediate risk (C), and high-risk (D) IPI groups.

Figure 4.

Two-year PFS Cox regression stratified for DS5 I-PET–positive patients and timing. Corrected for low-risk (A), low-intermediate risk (B), high-intermediate risk (C), and high-risk (D) IPI groups. For all risk groups, I-PET2–positive and I-PET3–positive regression curves are superimposed.

Figure 5.

Two-year PFS Cox regression stratified for ΔSUV_max I-PET–positive patients and timing. Corrected for low-risk (A), low-intermediate risk (B), high-intermediate risk (C), and high-risk (D) IPI groups.