PF297 COMPARISON OF RITUXIMAB DOSE‐ADJUSTED EPOCH (R‐DA‐EPOCH) WITH RITUXIMAB‐CHOP (R‐CHOP) CHEMOTHERAPY IN PRIMARY MEDIASTINAL LARGE B‐CELL LYMPHOMA (PMLBCL)
Authors: Vassilakopoulos T. , Mellios Z. , Verigou E. , Papageorgiou S. , Chatzidimitriou C. , Giatra H. , Kalpadakis C. , Gainaru G. , Karakatsanis S. , Xanthopoulos V. , Katrodritou E. , Tsirogianni M. , Arapaki M. , Giannikos T. , Katsaouni P. , Assimakopoulos I. , Liaskas A. , Constaninou E. , Bellia M. , Kourti G. , Leonidopoulou T. , Assimakopoulou T. , Karianakis G. , Symeonidis A. , Grentzelias D. , Sakellariou K. , Pappa V. , Papadaki E. , Plata E. , Bakiri M. , Angelopoulou M. , Konstantopoulos K. , Karmiris T. 
Published: June 2019

Background:

R‐da‐EPOCH provided excellent results in PMLBCL in a phase 2 NCI trial and appeared to obviate the need for consolidative radiotherapy (RT). However, there is no direct randomized comparison of R‐da‐EPOCH vs R‐CHOP. A recent retrospective comparison revealed a modest, non‐significant benefit in disease control but much less use of RT with R‐da‐EPOCH. However, the selection of each regimen was at the treating physician's discretion, so that bias was inevitably introduced.

Aims:

To compare the efficacy of R‐da‐EPOCH for disease control and omission of RT in PMLBCL compared to R‐CHOP.

Methods:

In 10 participating Centers in Greece, R‐da‐EPOCH was adopted at a certain timepoint for all patients with PMLBCL, while R‐CHOP (21‐day >> 14‐day schedule) had previously been the standard of care. Consolidative RT was used at the discretion of the treating physician. R‐CHOP controls (<65 years old) were selected from our database among consecutive patients treated at the same Centers, starting from the most recent patient and selecting, if possible, an equal number of R‐CHOP patients to those treated with R‐da‐EPOCH, going backwards. Thus, selection bias was minimized.

Results:

R‐da‐EPOCH was given in 52 consecutive patients (median follow‐up 17 months). Appropriate consecutive R‐CHOP‐treated controls were 43 (median follow‐up 34 months), because R‐da‐EPOCH‐treated patients were more than R‐CHOP‐treated ones in 3 participating Centers. The two groups (R‐da‐EPOCH and R‐CHOP) were absolutely: Age (median 30.5 vs 32), gender (female 69% vs 72%), B‐symptoms (31% vs 36%), performance status ≥2 (35% vs 23%; p = 0.21), stage III/IV (17% vs 12%), any extranodal involvement (27% vs 43%, p = 0.11), any serositis (49% vs 46%), bulky disease (71% vs 75%), LDH levels >twice normal (>2x; 41% vs 39%), anemia (48% vs 42%), leukocytosis ≥10x109/L (31% vs 27%), ESR ≥30 mm/h (78% vs 79%), albumin <4 g/dL (49% vs 45%), age‐adjusted IPI (aaIPI) ≥2 (39% vs 38%) (all p‐values >0.40, unless otherwise stated). Among R‐CHOP‐treated patients 10/43 had treatment failure compared to 5/52 for R‐da‐EPOCH. One R‐da‐EPOCH patient developed early‐onset acute leukemia with t(9;11) and was counted as event in event‐free survival (EFS) analysis. The 2‐year freedom from progression (FFP) was 89% vs 77% (p = 0.22), while the 2‐year EFS was 86% vs 77% (p = 0.35). With 5 deaths recorded (4 in R‐CHOP vs 1 in R‐da‐EPOCH; all disease related), the 3‐year overall survival (OS) was 96% vs 90% (p = 0.27). Among R‐CHOP‐treated patients, 5 did not receive RT due to chemorefractory disease; 29/38 potentially eligible patients (76%) received RT. Among 46 R‐da‐EPOCH‐treated patients who had completed final resonse assessment, 5 did not receive RT due to chemorefractory disease; only 6/41 potentially eligible patients (15%) received RT (p < 0.001). In multivariate analysis of FFP and EFS adjusting for any extranodal involvement and LDH >2x, only LDH >2x was an independent prognostic factor, while the R‐da‐EPOCH vs R‐CHOP difference remained non‐significant.

Summary/Conclusion:

We report here the least biased non‐randomized comparison between R‐da‐EPOCH and R‐CHOP conducted so far with well‐matched subgroups of consecutively treated patients. Incorporation of more R‐da‐EPOCH treated patients and appropriate controls is ongoing. Although the 2‐year FFP and EFS appeared to be less impressive than originally reported by the NCI group, R‐da‐EPOCH minimized the use of RT in a real‐life setting and provided numerically, but not statistically superior disease control than R‐CHOP for the time being.