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DA-EPOCH-R/HD-MTX for CD5+ DLBCL
Table 1. Baseline clinical features and disease characteristics.
Table 2. Morphological and immunophenotypical features. All patients (n=47)
Characteristic
Age, years Median Range >60 years
Sex Male Female
Stage II
III-IV
ECOG PS 0or1 >1
Serum LDH level Normal Elevated
Extranodal sites 0or1
>1
IPI risk category Low/Low-intermediate High-intermediate/High
CNS-IPI risk category Low
Intermediate
High Cell-of-origin*
ABC
GCB
Unclassified
All patients (n=47)
62 37-74 28 (60%)
18 (38%)
29 (62%)
20 (43%) 27 (57%)
45 (96%)
2 (4%)
16 (34%) 31 (66%)
31 (66%)
16 (34%)
25 (53%) 22 (47%)
14 (30%) 23 (49%) 10 (21%)
39 (85%)
4 (9%)
3 (7%)
Morphology
Common variant Giant cell rich variant Polymorphic variant Immunoblastic variant
Immunohistochemistry
CD5*
CD20
CyclinD1
CD10†
BCL6†
MUM1†
MYC†
BCL2†
MYC positive/BCL2 positive†
COO subtype by Hans' criteria GCB†
Non-GCB†
EBER in situ†
COO: cell-of-origin; EBER: Epstein-Barr virus-encoded RNA-1; GCB: germinal center-B-
cell-like. *Assessed by flow cytometry in 4 patients. †Examined in 46 patients.
cycles. Thrombocytopenia of <25x109/L occurred in 8% of cycles. Febrile neutropenia (FN) occurred in 66% of patients and 23% per cycle of DA-EPOCH-R (Table 3 and Online Supplementary Table S3). All patients who experi- enced FN recovered from the toxicity soon after initial antibiotics therapy. Possible second malignancies were documented in three patients (age, 64-74 years; acute myeloid leukemia, n=1; glioblastoma, n=1; and colon can- cer in adenoma, n=1). In two of these patients, the second malignancy was diagnosed after salvage chemotherapy for relapsed CD5+ DLBCL.
Discussion
To the best of our knowledge, this is the first clinical trial for CD5+ DLBCL. At the beginning of this trial in 2015, we calculated the threshold 2-year PFS using our previous retrospective study including 337 patients with CD5+ DLBCL. In 149 patients with newly diagnosed stage II-IV CD5+ DLBCL who received rituximab-containing chemotherapy (R-chemo) and had available follow-up data, the 2-year PFS was 51%. Recently, the results of sev- eral retrospective studies of CD5+ DLBCL in the ritux- imab-era (R-era) were reported. In both cohorts of 102 patients with all stage CD5+ DLBCL who received R-chemo at nine institutes in the United States10 and 31 patients with all stage CD5+ DLBCL who received R- CHOP in other Western countries,9 the 2-year OS was less than 50%. Therefore, we consider that our threshold set- ting was reasonable and that the 2-year PFS (79%) by the protocol treatment in our present study was superior to the historical control.
Few reports have described the use of DA-EPOCH-R for CD5+ DLBCL. For all DLBCL subtypes, there was no sig-
31 (66%) 3 (6%) 12 (26%) 1 (2%)
47 (100%) 47 (100%) 0 (0%) 13 (28%) 39 (85%) 44 (96%) 26 (57%) 45 (98%) 26 (57%)
13 (28%)
33 (72%)
0 (0%)
ABC: activated B-cell-like; CNS: central nervous system; EBER: Epstein-Barr virus-encod- ed RNA-1. GCB: germinal center-B-cell-like; IPI: International Prognostic Index; PS: per- formance status. *Examined by Lymph2Cx using formalin-fixed and paraffin-embed- ded tissues (n=46).
ment was discontinued after the first drug administration due to grade 4 TLS. CNS relapses occurred in two patients (one patient had leptomeningeal disease with tumor of ethmoid sinus, and the other patient had brain parenchy- mal disease alone) before HD-MTX of the protocol treat- ment.
Toxicity
Toxicity was assessed in all 445 cycles of DA-EPOCH- R/HD-MTX with 357 cycles of DA-EPOCH-R in all 47 patients. Table 3 lists adverse events in all 445 cycles of DA-EPOCH-R/HD-MTX, and Online Supplementary Table S3 lists adverse events in 357 cycles of DA-EPOCH-R. There were no treatment-related deaths. The most com- mon grade 3 non-hematologic toxicity was elevated ALT (28%). Four patients experienced grade 3 infection, includ- ing catheter-related infection, cellulitis, endocarditis, and urinary tract infection. Grade 3 peripheral motor neuropa- thy and peripheral sensory neuropathy occurred in 4% of patients, separately. There was no grade 3 cardiac toxicity. Grade 4 neutropenia and thrombocytopenia were present in 98% and 26% of patients, respectively.
The targeted ANC (<0.5x109/L) occurred in 77% of
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