Abstract
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 (
Patient Characteristics
| Characteristics | All Patients | DA-EPOCH | DA-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%) |
| Characteristics | All Patients | DA-EPOCH | DA-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%) |
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.
Figure
Disclosures: Chemotherapy agents for untreated aggressive lymphoma. These are not all approved specifically for this indication.
