PMBL is a distinct clinicopathologic entity characterized by young age, female preponderance, localized disease, prominent sclerosis and CD30+. Gene expression profiling reveals a unique molecular signature, distinct from other DLBCL subtypes, with similarity to classical Hodgkin lymphoma (HL) (J Exp Med 198: 851, 2003). HL is typically CD20 negative whereas PMBL has robust CD20 staining. As with HL, the risk of local failure after anthracycline-based therapy in PMBL has led to routine mediastinal radiation. Given the young median age, female predominance and high cure rates, long-term toxicities from secondary malignancies and coronary artery disease can be life threatening. We prospectively evaluated the role of DA-EPOCH± R without routine radiation in 44 patients with untreated PMBL. The first 18 patients received DA-EPOCH alone and the subsequent 26 received DA-EPOCH+R. DA-EPOCH was administered for 6–8 cycles as described (

Blood99: 2685, 2002
). Most patients had adverse prognostic features with bulky disease, elevated LDH and extranodal sites, which were balanced among the 2 groups.

Patient Characteristics

CharacteristicsAll PatientsDA-EPOCHDA-EPOCH-R
Total Patients 44 18 26 
Gender (F/M) 26:18 (1.44) 10:8 (1.25) 19:9 (1.88) 
Median age, y (range) 34 (12–70) 34 (20–62) 34 (12–70) 
Median Mass cm (range) 9.8 (3–19.7) 8.4 (5.1–15.7) 10.2 (3–19.7) 
Bulky mass > 6 cm 34 (83%) 13 (87%) 21 (81%) 
ECOG PS > 1 4 (9%) 2 (11%) 2 (8%) 
Stage III or IV 19 (43%) 9 (50%) 10 (38%) 
LDH > Normal 32 (73%) 14 (78%) 18 (69%) 
Extranodal sites 25 (57%) 9 (50%) 16 (63%) 
Pleural effusion 15 (34%) 4 (22%) 11(42%) 
CharacteristicsAll PatientsDA-EPOCHDA-EPOCH-R
Total Patients 44 18 26 
Gender (F/M) 26:18 (1.44) 10:8 (1.25) 19:9 (1.88) 
Median age, y (range) 34 (12–70) 34 (20–62) 34 (12–70) 
Median Mass cm (range) 9.8 (3–19.7) 8.4 (5.1–15.7) 10.2 (3–19.7) 
Bulky mass > 6 cm 34 (83%) 13 (87%) 21 (81%) 
ECOG PS > 1 4 (9%) 2 (11%) 2 (8%) 
Stage III or IV 19 (43%) 9 (50%) 10 (38%) 
LDH > Normal 32 (73%) 14 (78%) 18 (69%) 
Extranodal sites 25 (57%) 9 (50%) 16 (63%) 
Pleural effusion 15 (34%) 4 (22%) 11(42%) 
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IHC profiling was similar in both groups and consistent with gene expression profiling of PMBL. Analysis of 40 cases showed CD20+ 40/40 (100%), CD10+ 2/30 (7%), BCL-6+ 21/26 (81%), MUM-1+ 10/24 (42%) and high MIB-1 with median (range) of 82% (54–98). At a median potential follow-up of 9.5 and 4.2 years, EFS and OS are shown below for DA-EPOCH and DA-EPOCH-R, respectively. Rituximab was associated with a significantly improved EFS (p=.038) and OS (p=0.023) by 2-tailed exact log-rank test with caveats associated with any non-randomized comparison. Three patients on DA-EPOCH-R had positive PET and biopsy after treatment. One received radiation (event), one recieved salvage chemotherapy and radiation (event), and one no further treatment after biopsy. DA-EPOCH-R is highly effective in PMBL with OS of 100% and obviated the need for radiation/surgery in 23/26 (88%) patients. Rituximab may significantly improve EFS and OS with DA-EPOCH-based treatment. Accrual continues.

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Figure

Topics:
epoch protocol, primary mediastinal large b-cell lymphoma, rituximab, biopsy, cd20 antigens, extranodal disease, gene expression profiling, anthracycline antibiotics, chemotherapy regimen, coronary arteriosclerosis

Disclosures: Chemotherapy agents for untreated aggressive lymphoma. These are not all approved specifically for this indication.

Author notes

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Corresponding author

2006, The American Society of Hematology
2006
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