Page 193 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

R-CHOP with lenalidomide in MYC+ LBCL
Observational analysis: predictive value of iPET-CT
At iPET-CT after three cycles of R2CHOP, 57 of 82 patients (70%) were in CMR; of these 45 of 57 (79%) were still in CMR and 11 of 57 (19%) showed PMD at EOT PET-CT, and one missed EOT evaluation (Table 2). 23 of 82 patients (28%) were in PMR at iPET-CT; 10 of 23 (43%) of these converted to CMR, 4 of 23 (17%) remained in PMR, 9 of 23 (39%) showed PMD at EOT. The PPV of iPET-CT for predicting EOT PET-CT result was 60% (15 of 25), the NPV 79% (45 of 57) (Online Supplementary Table S3B).
Discussion
From retrospective series it is clear that first-line R-CHOP therapy is not sufficiently effective for patients with MYC+ LBCL with CR rates of 40-50% and 3-year OS rates of 35% only [6,8]. Intensified chemotherapy regimens such as R-CODOX-M/R-IVAC or autologous stem cell transplantation have not improved OS, and result in increased toxicity [5,9-11].
We designed a prospective clinical trial for MYC+ LBCL patients, in which a time window of one cycle of R-CHOP was allowed to perform molecular diagnostics. This approach permitted high risk patients to start treatment immediately and overcame the bias of inclusion of mainly lower risk patients due to enrolment delays [25]. In this trial we show that the addition of lenalidomide to R-CHOP resulted in EOT CMR rate of 67% CMR and 2-year survival rates of 73%, 75%, and 63% for OS,DFSandEFSrespectively.Toourknowledge,thisisthesecondprospectivetrial especially designed for MYC+ LBCL patients. Recently, Dunleavy and colleagues reported a single arm phase II study in which the efficacy of DA-EPOCH-R for MYC+ LBCL patients was explored [12]. Results for EOT CMR and survival rates are largely comparable between both approaches with EOT CMR rate of 74%, 4-year OS rates of 77% and EFS of 71% in the study of Dunleavy. When compared to the trial of Dunleavy, our patient population was larger (82 vs. 53 patients), comparable in age (median 63 vs. 61 years) but included more patients with IPI ≥3 (65% vs. 49%) and more patients with DH/TH (65% vs. 45%). Regarding safety, grade 3/4 infections were seen in 24% of cycles with DA-EPOCH-R versus grade 3 (and no grade 4 infections) in only 2,8 % of cycles (18 episodes) with R2CHOP. DA-EPOCH-R resulted in three treatment related deaths vs. none with R2CHOP.
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