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DA-EPOCH-R versus R-CHOP for double hit DLBCL
On 10 January 2019, Anna Dodero and Anna Guidetti from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, IT, and colleagues published in Leukemia a retrospective study investigating the efficacy and safety of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in double-hit diffuse large B-cell lymphoma (DLBCL) patients.
In this retrospective study the outcomes of DLBCL double expressors were compared after DA-EPOCH-R or R-CHOP treatment, which was administered in a similar period in three different Italian institutions. The primary endpoints of this study were progression-free survival (PFS), and overall survival (OS). Secondary endpoints included survival comparisons according to different subgroup analyses (age, genetic abnormalities etc.).
Study design & baseline characteristics
- N = 114 double-hit DLBCL patients
- Patients were treated with either:
- DA-EPOCH-R (n = 51)
- R-CHOP (n = 63)
- Dosing:
- DA-EPOCH-R (n = 51; six 21-cycles):
- Etoposide: 50 mg/m2 intravenously (IV) on Day 1, 2, 3, and 4
- Doxorubicin: 10 mg/m2 IV on Day 1, 2, 3, and 4
- Vincristine: 0.4 mg/m2 IV on Day 1, 2, 3, and 4
- Cyclophosphamide: 750 mg/m2 IV on Day 5
- Prednisone: 60 mg/m2 orally on Day 1, 2, 3, 4 and 5
- R-CHOP (n = 63): usual dosing every 21 days
- DA-EPOCH-R (n = 51; six 21-cycles):
- Central nervous system (CNS) prophylaxis was administered when necessary according to institutional guidelines
- Patients in the R-CHOP group received less CNS prophylaxis (30%) than those in the DA-EPOCH-R group (96%)
- All patients underwent computed tomography (CT) scan, positron emission tomography scan (PET), bone marrow (BM) biopsy and diagnostic lumbar puncture, including cytological and immunophenotypic analyses at baseline
- An intermediate CT was performed after 3−4 DA-EPOCH-R or R-CHOP cycles
- Patients exhibiting a less than partial response (PR) or disease progression (PD) were moved to second line regimens according to institutional guidelines
- Clinical response evaluation was performed at the end of treatment cycle 6 by CT, PET, and BM biopsy
- Disease assessment was performed at follow-up (three month intervals) for the first two years; every six months until the fifth year; annually thereafter
- Baseline characteristics were well balanced between the two groups
Key findings
- CNS relapses:
- DA-EPOCH-R: n = 1 patient
- R-CHOP: n = 3 patients
- Consolidative radiotherapy administration:
- DA-EPOCH-R: 21% of patients
- R-CHOP: 35% of patients
- DA-EPOCH-R group median follow-up: 20 months
- R-CHOP group median follow-up: 49 months
- Two-year PFS (before inverse probability of treatment weight [IPTW] Cox modelling):
- DA-EPOCH-R: 62% (95% CI, 45−84%)
- R-CHOP: 54% (95% CI, 43−69%)
- Two-year OS (before IPTW Cox modelling):
- DA-EPOCH-R: 85% (95% CI, 74−98%)
- R-CHOP: 70% (95% CI, 60−83%)
- Two-year PFS (after IPTW Cox modelling):
- DA-EPOCH-R: 57%
- R-CHOP: 51%
- Comparison: P = 0.198
- Two-year OS (after IPTW Cox modelling):
- DA-EPOCH-R: 90%
- R-CHOP: 67%
- Comparison: P = 0.07
- IPTW Cox modelling was used to investigate the effect of patient age, International Prognostic Index (IPI) or DLBCL molecular subgroup on patient outcomes:
- Age was the only statistically significant influencing variable. In patients aged < 65 years:
- DA-EPOCH-R:
- PFS: 82% (95% CI, 66−100%)
- OS: 90% (95% CI, 74−100%)
- R-CHOP:
- PFS: 43% (95% CI, 26−73%)
- OS: 62% (95% CI, 43−88%)
- PFS comparison: P = 0.02
- OS comparison: P = 0.04
Safety
- Death occurred in:
- DA-EPOCH-R: 12% of patients (n = 6)
- PD: n = 4
- Pneumonia: n = 1
- Suicide: n = 1
- R-CHOP: 35% of patients (n = 22)
- PD: n = 20 patients
- Drug toxicity: n = 2 patients
- Treatment discontinuation due to adverse events (AEs) occurred in:
- DA-EPOCH-R: n =2 patients (pneumonia [Grade 5] and infection [alive patient in CR])
- R-CHOP: n = 2 patients (both Grade 5 drug toxicity)
- EPOCH dose adjustment was performed successfully in the majority of patients aged ≤ 65 years (73% of patients escalated to ≥ 3 dose level). However, the majority of patients > 65 years received only dose level one of EPOCH
- DA-EPOCH-R: 12% of patients (n = 6)
Conclusions
- Age and genetic abnormalities play a key role in patient outcomes of DLBCL double expressors
- DA-EPOCH-R treatment was associated with a better PFS than R-CHOP in young double-hit DLBCL patients (< 65 years old)
- DA-EPOCH-R treatment was associated with a better OS than R-CHOP in young double-hit DLBCL patients (< 65 years old)
- Patient subgroup analysis for genetic abnormalities revealed that DA-EPOCH-R leads to a better PFS than R-CHOP in such patient populations
References