Page 183 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

R-CHOP with lenalidomide in MYC+ LBCL
these patients, only a single MYC rearrangement is found (single hit [SH]), while in 70% MYC rearrangement is detected together with either a BCL2 or BCL6 rearrangement (double hit [DH]: MYC+/BCL2+ or MYC+/BCL6+) or with both (triple hit [TH]: MYC+/BCL2+/BCL6+) [4]. It has been shown that in patients with MYC+ LBCL, standard first-line therapy with R-CHOP results in an inferior prognosis compared to those without MYC rearrangement (2-year OS 35% vs. 61% [8] and 5-year OS 31% vs. 66% [6]). Moreover, patients with MYC+ LBCL have an increased risk of central nervous system (CNS) relapse [5,6]. Recently, Rosenwald et al. demonstrated that the inferior prognosis of MYC rearranged patients is however largely observed in patients with DH/TH lymphoma [7]. In the revised World Health Organisation (WHO) 2017 classification, SH is not recognized as a separate entity in contrast to DH/TH lymphoma [1].
In search for improvement, intensified chemotherapy regimens, such as hyper- CVAD and R-CODOX-M/R-IVAC, have been investigated. Data mainly come from subanalyses of MYC rearrangement positive patients in trials designed for unselected DLBCL patients. These studies indicate that intensified treatment results in improvement of progression free survival (PFS), but not OS [9-11]. Only recently, a prospective, multicenter, single arm phase II study specifically designed for MYC+ LBCL patients showed that DA-EPOCH-R resulted in a promising CMR rate at end of treatment (EOT) of 74% and 4 year EFS and OS of 71% and 77%, respectively [12].
Lenalidomide is an oral immunomodulatory drug with direct antitumor effects and indirect effects on the tumor microenvironment [13]. In vitro studies have demonstrated that lenalidomide exposure results in down-regulation of MYC and its target genes via cereblon and IRF4 in lymphoid cells, thereby providing the rationale for introducing lenalidomide as a therapeutic option in MYC+ LBCL [14].Two phase II studies in ABC/non-GCB-subtype DLBCL have demonstrated that the addition of lenalidomide to R-CHOP (R2CHOP) is indeed feasible and may contribute to a favorable outcome by decreasing CNS relapse [15,16]. Against expectation, R2CHOP did not result in a survival advantage in ABC-subtype DLBCL, as has recently been shown in a phase III study (ROBUST) [17].
The present study reports the results of a prospective single-arm phase II trial for MYC+ LBCL patients treated with R2CHOP. Patients were identified through a nationwide molecular biomarker diagnostics program. We report outcome based on
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