Page 212 - Haematologica May 2020

F. Schieppati et al.
P=0.41). Median OS and PFS at three years were 58.8% and 54.8%, respectively, with no significant differences between the groups treated with intensified or standard regimens (P=0.93 and P=0.69, respectively). Outcome was similar in the two groups receiving standard or intensified regimens, despite the different treatment schemes. Twenty patients received R-COMP due to age over 70 years or car- diac dysfunction; none received consolidation with ASCT. The other 26 patients in the standard regimen arm received R-CHOP, and no differences in the outcome were seen between patients treated with the R-COMP and those treated with R-CHOP (OS 73% vs. 53%, P=0.2). In the intensified group, one patient with a transformed lym- phoma received R-ESHAP and ASCT due to the risk of car- diotoxicity related to prior anthracycline therapy. There was no significant difference in OS among patients receiv- ing R-CHOP-like + ASCT, GMALL-like ± ASCT, or R-DA- EPOCH ± ASCT (OS 69% vs. 51% vs. 69%, respectively, P=0.8).
Table 1. Clinical characteristics of the patients with structural and numerical aberrations of MYC at fluorescence in situ hybridization.
MYC, BCL2 and BCL6 translocations
A MYC translocation (MYC-T) by FISH study was
observed in 34 patients (8.8%). With respect to BCL2 and BCL6, MYC translocation occurred as a single-hit (SH) aber- ration in 9 of 34 patients (26%), whereas 19 (56%) and 6 (18%) patients had a “double-hit” (DH) and “triple-hit” (TH) DLBCL, respectively. The clinical characteristics in terms of age, gender, histopathology, MYC protein expression by IHC, Ann Arbor and IPI stage were not significantly differ- ent among patients with SH, DH or TH DLBCL (Table 2). Three patients who received palliative/symptomatic treat- ment were excluded from the survival analyses. Overall, nine patients were treated with a standard regimen and 22 with an intensified regimen, with similar distribution among the SH, DH and TH DLBCL groups. After a median follow up of 33 months, the 2.5-year OS was similar among SH, DH, and TH DLBCL patients.
Numerical aberrations MYC by fluorescence in situ hybridization
We observed an increased number of MYC gene copies (16%) in tumor samples from 61 patients negative for MYC translocations. Fifty-seven cases (15%) were referred to as to “increased copy number of MYC” (MYC- ICN) DLBCL, while four cases (1%) showed amplification of MYC (MYC-AMP) (Figure 1). The exact number of
Table 2. Clinical characteristics of the patients with single-hit (SH), double-hit (DH) or triple-hit (TH) diffuse large B-cell lymphoma at fluorescence in situ hybridization.
Age, median (range)
Male sex
Ann Arbor stage III-IV
IPI High intermediate/
High risk
IHC MYC positivity
Histopathology DLBCL, NOS BCLU
BCL2 and BCL6 status BCL2-T
BCL6-T
BCL2-ICN
BCL6-ICN
Treatment regimen Standard
R-CHOP/R-CHOP-like - R-CHOP
- R-COMP
Intensified
GMALL-like ± ASCT R-DA-EPOCH ± ASCT R-CHOP/R-CHOP-like + ASCT
All patients (n =95) n (%)
67 (21-88)
63 (66) 76 (80)
66 (69)
n=52
46 (88)
87 (92)
8 (8)
34 (36) 29 (31) 23 (24) 21 (22)
46 (48) 26 (27) 20 (21)
44 (46) 15 (23) 13 (14) 16 (17) 15 (16)
MYC-T (n=34) n (%)
66.5 (27-88)
24 (71) 30 (88)
24 (71)
n=24
24 (100)
27 (79)
7 (21)
20 (59) 2 (6) 11 (32) 5 (15)
9 (26) 6 (17) 3 (9)
22 (65) 10 (29) 10 (29) 2 (6)
MYC-ICN/ MYC AMP (n=61) n (%)
67 (21-84)
39 (64) 46 (75)
42 (69)
n=28
21 (75)
60 (98)
1 (2)
14 (23) 27 (44) 12 (20) 16 (27)
37 (61) 20 (33) 17 (28)
22 (36) 5 (8) 3 (5) 14 (23) 14 (23) 0
2 (3)
15 (25)
n=59
37 (63) 8 (14) 14 (24)
MYC-T SH MYC-T DH MYC-T TH P (n=9) (n=19) (n=6)
n(%) n(%) n(%)
Age, median (range)
Male gender
Ann Arbor stage III-IV
IPI High intermediate/
High risk
IHC MYC positivity
Histopathology DLBCL, NOS BCLU
Treatment regimen Standard
R-CHOP/R-CHOP-like
Intensified GMALL-like ± ASCT R-DA-EPOCH ± ASCT R-CHOP/R-CHOP-like
Palliative
71 (29-74)
4 (44) 7 (78) 8 (89)
n=5
5 (100)
7 (78)
2 (22)
2 (22)
4 (45) 0
+ ASCT 1 (11)
2 (22)
63 (29-88)
15 (79) 18 (95) 12 (63)
n=15
15 (100)
15 (79)
4 (21)
4 (21)
5 (27) 8 (42) 1 (5)
1 (5)
6 (36)
n=18
9 (50)
4(22) 0 0.16 5 (28) 2 (33) 0.89
58% 62% 0.96
- R-CHOP + ASCT
-R-ESHAP+ASCT 1(1) 1(3)
62 0.71 (58-83)
5 (83) 0.13 5 (83) 0.39 4 (67) 0.36
n=4 - 4 (100)
5 (83) 0.96
1 (17)
3 (50) 0.35
1 (17) 0.46 2 (33) 0.07 0 0.65
0 0.23 1 (17) 0.44
n=6
1 (3)
Palliative
Total ASCT consolidation
Response CR
PR
NR/disease progression
5 (5)
23 (24)
n=90
55 (61) 12 (13) 23 (26)
3 (9)
8 (23)
n=31
18 (58) 4 (13) 9 (29)
Total ASCT consolidation 1 (11)
Response n=7
CR 5 (71) PR 0 NR/disease progression 2 (29)
2.5-year OS 47%
4 (67) 0.69
DLBCL: diffuse large B-cell lymphoma; NOS: not otherwise specified; BCLU: B-cell lym- phoma, unclassifiable; IPI: International Prognostic Index; IHC: immunohistochem- istry; ASCT: autologous stem cell transplantation; CR: complete response; PR: partial response; NR: no response; n: number.
DLBCL: diffuse large B-cell lymphoma; NOS: not otherwise specified; BCLU: B-cell lymphoma, unclassifiable; IPI: International Prognostic Index; IHC: immunohistochemistry; ASCT: autologous stem cell transplantation; CR: complete response; PR: partial response; NR: no response; OS: over- all survival; n: number.
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