Page 194 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 7
Lenalidomide penetrates the CNS, and thereby may aid to prevent CNS relapses as has been suggested for nongerminal center B-cell (GCB) subtype lymphoma patients treated with R2CHOP [15]. Indeed, in this study, which combined lenalidomide and intrathecal prophylaxis, a remarkably low rate of CNS relapse at a median follow-up of 25.4 months was seen (n=1).
Several remarks regarding our study can be made. First, although correlation CMR at EOT PET-CT with survival in MYC+ LBCL has been described in a retrospective study [26], one might argue that it is not an ideal primary endpoint. Given the high FDG-avidity of MYC+ LBCL and the fact that CMR at EOT PET-CT in our study was highly predictive for DFS (NPV of 93%), we feel that using CMR at EOT PET-CT as a surrogate endpoint for highly aggressive B-cell lymphomas such as MYC+ LBCL is justified.
Second, clinical prognostic markers, including age, stage, IPI score, as well as COO were not significantly correlated to CMR on EOT PET-CT and survival, which might be explained by the inclusion of high risk patients; 65% of our patients have an IPI score of ≥3, versus only 27% in Ziepert’s meta-analysis of the value of IPI in the rituximab era [2].
Furthermore, our patient population included patients with SH lymphoma (24%) based on previous reports demonstrating poor prognosis of these patients following R-CHOP [5,6,8,27]. However, in the revised WHO 2017 classification, SH is not recognized as a separate entity in contrast to DH/TH lymphoma. Recently, Rosenwald et al. demonstrated that the inferior prognosis of MYC rearranged patients is largely observed in patients with DH lymphoma [7]. However, SH patients still have a worse prognosis compared to patients without a MYC rearrangement, although this is not statistically significant when regarding OS (P=0.077). Our trial was not powered to study the prognostic impact of SH versus DH/TH in the R2CHOP setting.
Finally, we explored the role of iPET-CT scanning as a tool for early identification of refractory MYC+ LBCL. In non-selected cases of DLBCL, CMR on iPET- CT after two to four R-CHOP cycles has a high NPV for 2-year PFS, but the PPV varies widely [28]. In our study, the PPV of iPET-CT for achievement of CMR on EOT PET-CT was only 60% and therefore does not support the use
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