Contributions
Abstract: EP551
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Further to the impressive results with R-da-EPOCH in a phase 2 NCI trial, retrospective comparisons have shown a modest, non-significant benefit in disease control but also a reduced need for consolidative radiotherapy (RT) administration with R-da-EPOCH vs R-CHOP in PMLBCL. However, the choice of treatment was at the discretion of the treating physician, inevitably introducing systematic bias.
Aims
To compare the efficacy of R-da-EPOCH vs R-CHOP with an as much as possible unbiased selection of controls and to investigate the physicians’ compliance with the dose escalation protocol in routine practice.
Methods
R-da-EPOCH was adopted as the treatment of choice in all consecutive patients with PMLBCL <60 years (n = 86) in 16 participating Centers in Greece, all of which administered R-CHOP as standard of care until then. The first control group (CG) of R-CHOP-treated patients (CG-1) was devised without any bias from the same Centers’ patient database, selecting in reverse chronological order an equal number of patients to those treated with R-da-EPOCH at the same Center if possible, thus minimizing selection bias. Due to lack of an equal number of controls (13 patients less in the R-CHOP arm) and the administration of R-CHOP-14 to 18 patients in 5/16 Centers, the core group of 55 patients was maintained (86-13-18=55) and 2 more R-CHOP-21 CGs were devised. In CG-2, the 31 missing patients were replaced by 27 patients all treated at Nicosia General Hospital, Cyprus. In CG-3, 29 consecutive patients from 4 already participating Centers of similar care services capacity to the 4/5 aforementioned Centers were included, and 2 from another similarly suitable Center. Hence, all 86 CG-3 patients had received R-CHOP-21 and were consecutively selected from a previously created patient list.
Results
The groups of R-da-EPOCH-treated patients and R-CHOP CG-1 (n = 73), CG-2 (n = 82) and CG-3 (n = 86) were comparable at baseline except for worse PS in the former. Two patients developed acute myeloid leukemia (AML) 10.4 and 22 months after starting R-da-EPOCH and having reached dose escalation levels 6 and 4, respectively. The 5-year freedom from progression (FFP), event-free survival (EFS) and overall survival (OS) rates did not differ significantly and are shown in table 1 [there was a marginal difference regarding FFP only in comparison to CG-3 (p = 0.06)], while RT was administered to far fewer potentially eligible for RT patients in the R-da-EPOCH group. In the multivariate analysis of FFP, the difference between R-da-EPOCH and R-CHOP remained non-significant when comparing to CG-1 and CG-2 but became statistically significant when compared to CG-3 [p = 0.035, HR = 0.40 (0.16 - 0.94)]. Only 40 (61%) out of the 65 patients who had completed R-da-EPOCH and had available data received the regimen completely according to the protocol, reflecting real-world data on R-da-EPOCH administration. These patients had a 5-year FFP ratio of 92% and 55% of them had reached ≥4 dose escalation level (Table 1), similarly to the original NCI study.
Conclusion
This comparative study between R-da-EPOCH and R-CHOP carried the least possible systematic error in the retrospective setting. Five-year FFP and EFS rates appeared less impressive than initially reported and 2 AML cases have been reported so far. However, R-da-EPOCH minimized the need for RT and demonstrated a numerically better disease control. Finally, in real-world situations, R-da-EPOCH is seemingly not given lege artis in a considerable proportion of patients.
Keyword(s): Chemotherapy, Radiotherapy
Abstract: EP551
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Further to the impressive results with R-da-EPOCH in a phase 2 NCI trial, retrospective comparisons have shown a modest, non-significant benefit in disease control but also a reduced need for consolidative radiotherapy (RT) administration with R-da-EPOCH vs R-CHOP in PMLBCL. However, the choice of treatment was at the discretion of the treating physician, inevitably introducing systematic bias.
Aims
To compare the efficacy of R-da-EPOCH vs R-CHOP with an as much as possible unbiased selection of controls and to investigate the physicians’ compliance with the dose escalation protocol in routine practice.
Methods
R-da-EPOCH was adopted as the treatment of choice in all consecutive patients with PMLBCL <60 years (n = 86) in 16 participating Centers in Greece, all of which administered R-CHOP as standard of care until then. The first control group (CG) of R-CHOP-treated patients (CG-1) was devised without any bias from the same Centers’ patient database, selecting in reverse chronological order an equal number of patients to those treated with R-da-EPOCH at the same Center if possible, thus minimizing selection bias. Due to lack of an equal number of controls (13 patients less in the R-CHOP arm) and the administration of R-CHOP-14 to 18 patients in 5/16 Centers, the core group of 55 patients was maintained (86-13-18=55) and 2 more R-CHOP-21 CGs were devised. In CG-2, the 31 missing patients were replaced by 27 patients all treated at Nicosia General Hospital, Cyprus. In CG-3, 29 consecutive patients from 4 already participating Centers of similar care services capacity to the 4/5 aforementioned Centers were included, and 2 from another similarly suitable Center. Hence, all 86 CG-3 patients had received R-CHOP-21 and were consecutively selected from a previously created patient list.
Results
The groups of R-da-EPOCH-treated patients and R-CHOP CG-1 (n = 73), CG-2 (n = 82) and CG-3 (n = 86) were comparable at baseline except for worse PS in the former. Two patients developed acute myeloid leukemia (AML) 10.4 and 22 months after starting R-da-EPOCH and having reached dose escalation levels 6 and 4, respectively. The 5-year freedom from progression (FFP), event-free survival (EFS) and overall survival (OS) rates did not differ significantly and are shown in table 1 [there was a marginal difference regarding FFP only in comparison to CG-3 (p = 0.06)], while RT was administered to far fewer potentially eligible for RT patients in the R-da-EPOCH group. In the multivariate analysis of FFP, the difference between R-da-EPOCH and R-CHOP remained non-significant when comparing to CG-1 and CG-2 but became statistically significant when compared to CG-3 [p = 0.035, HR = 0.40 (0.16 - 0.94)]. Only 40 (61%) out of the 65 patients who had completed R-da-EPOCH and had available data received the regimen completely according to the protocol, reflecting real-world data on R-da-EPOCH administration. These patients had a 5-year FFP ratio of 92% and 55% of them had reached ≥4 dose escalation level (Table 1), similarly to the original NCI study.
Conclusion
This comparative study between R-da-EPOCH and R-CHOP carried the least possible systematic error in the retrospective setting. Five-year FFP and EFS rates appeared less impressive than initially reported and 2 AML cases have been reported so far. However, R-da-EPOCH minimized the need for RT and demonstrated a numerically better disease control. Finally, in real-world situations, R-da-EPOCH is seemingly not given lege artis in a considerable proportion of patients.
Keyword(s): Chemotherapy, Radiotherapy