Page 214 - Haematologica May 2020
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F. Schieppati et al.
  gression rate (7% vs. 41%, P=0.0009). In the MYC-ICN ≤4 subgroup, there was neither a difference in terms of ORR and CRR achievement, nor a significant advantage in terms of OS and PFS between patients treated with standard or intensified regimens. At a median follow up of 3.5 years, OS was 73% and 70%, respectively. In the MYC-T group, ORR was similar in patients treated with standard or inten- sive induction therapy, and CRR was slightly higher in the intensified-regimen group (64% vs. 55%) (Table 3).
Patients with MYC-ICN >4 and MYC-T receiving a first-line intensified regimen showed a non-significant trend toward a better outcome (2.5-year OS of 40% for standard treatment vs. 60% for intensified treatment in MYC-ICN >4; OS of 53% for standard treatment vs. 65% for intensified treatment in MYC-T). The same trend was seen combining MYC-AMP group with MYC-ICN >4 and MYC-T groups (2.5-year OS of 32% for standard vs. 57% for intensified treatment).
Table 3. Clinical characteristics of the patients with MYC-ICN ≤4, MYC-ICN >4, MYC-T, and MYC-AMP.
 protein expression by IHC, Ann Arbor and IPI stage, were not significantly different, except that patients with a his- tological diagnosis of BCLU clustered in the MYC-T and MYC-AMP groups (P=0.03) (Table 3). Notably, all patients with MYC-AMP showed aggressive clinical features, although one did not show MYC protein overexpression by IHC.
The treatment type and the response to treatment in each FISH category are reported in Table 3. Patients with MYC-ICN preferentially received standard treatment (61% MYC-ICN ≤4 and 65% MYC-ICN >4, respectively, P=0.008), unlike patients with MYC-T and MYC-AMP who received an intensified regimen in 65% and 75% of cases, respectively (P=0.02).
Patients with MYC-ICN ≤4 had a higher overall response rate (ORR) and complete response rate (CRR) compared to the other FISH groups (ORR 93% vs. 59%, P=0.0009; CRR 73% vs. 57%, P=0.16), and also a significantly lower pro-
      All patients
Age, median (range)
Male gender, n. (%)
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 + ASCT
Palliative
Total ASCT consolidation
Response ORR
Standard Intensified
CR Standard Intensified
PR Standard Intensified
NR/disease progression Standard
Intensified
MYC-ICN ≤4 MYC-ICN >4 MYC-T MYC-AMP P (n=31) (n=20) (n=34) (n=4)
n(%) n(%) n(%) n(%)
  65 (21-84)
20 (65)
22 (71)
19 (61)
n=13
9 (69)
31 (100)
73 (30-81)
9 (45)
15 (75)
16 (80)
n=11
9 (81)
20 (100)
66.5 (27-88)
24 (72)
30 (91)
24 (72)
n=24
24 (100)
27 (82)
66 (57-73) 0.81
4 (100) 0.15 4 (100) 0.77 4 (100) 0.31
n=3 0.21 2 (66)
3 (75) 0.06
1(25) 0.03
       0 0 6(18)
19 (61)
11 (35) 1 (3) 0
10 (33)
1 (3)
10 (33)
n=30
28 (93) 17/19 (89) 11/11 (100)
3/19 (16) 3/11 (27)
2 (7) 2/19 (10) 0/11 (0)
13 (65)
6 (30) 2 (10) 2 (10) 2 (10)
1 (5)
2 (11)
n=19
11 (63) 8/13 (61) 3/6 (50)
0/13 0/6
8 (42) 5/13 (38) 3/6 (50)
9 (26)
22 (65) 10 (29) 10 (29) 2 (6)
3 (9)
8 (23)
n=31
20 (64) 6/9 (67) 14/22 (64)
1/9 (11) 0/22
11 (36) 3/9 (33) 8/22 (36)
1 (25)
3 (75) 0.02
1 (25) 0.16* 0/1 (0)
1/3 (33)
6(20) 0 1(3) 0 0.03*
22 (73) 14/19 (74) 8/11 (73)
11 (58) 8/13 (61) 3/6 (50)
19 (61) 5/9 (55) 14/22 (64)
0.008 1 (25) 0.02
1 (25)
1 (25) 0.03
0 0.74 1 (25) 0.38
0/1 0/3
3 (75) 0.0009* 1/1 (100)
2/3 (67)
0.008
  n=4
1 (25) 0 1/3 (33)
0.0009*
 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; ORR: overall response rate; CR: complete response; PR: partial response; NR: no response; n: number. *Overall response (OR), CR, PR and NR/disease progression rates of MYC-ICN<4 compared to the combination of other fluorescence in situ hybridization (FISH) groups.
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