Page 148 - Haematologica May 2022

A. Dodero et al.
Table 2. Kaplan-Meier estimates of 2-year progression-free and overall survival according to patients and disease characteristics
Age ≤60
>60 Sex
Male
Female
Cell of origin**
Germinal central B cell
Non-Germinal central B cell Rearrangements
DEL DEL-BCL2 DEL-MYC DEL-DH/TH
Staging I-II
III-IV
International prognostic index
0-2
3-5
CNS prophylaxis
None
Intrathecal methotrexate Intravenous methotrexate
TP53 mutation*** Wild-type Mutated
2-year PFS (95% CI)
80.0 (70.4; 90.9) 67.7 (55.6; 82.4)
66.3 (55.9; 78.7) 87.1 (77.0; 98.7)
70.6 (59.1; 84.4) 74.6 (63.2; 87.9)
74.8 (64.9; 86.3) 69.2 (48.2; 99.5) 100
63.2 (44.8; 89.0)
91.8 (81.6; 100) 69.8 (60.6; 80.4)
88.1 (79.6; 97.6) 62.2 (50.7; 76.3)
50.8 (28.6; 90.2) 69.5 (56.5; 85.5) 81.8 (72.0; 93.0)
79.9 (68.9; 92.8)
58.3 (37.3; 91.1)
P* 2-year OS (95% CI) 0.138
P* 0.064
0.094
0.907 0.058
0.081 0.002
0.008
0.036
0.012
0.544 0.203
0.048 0.002
0.027
0.033
88.4 (80.0; 97.7) 78.2 (66.9; 91.3)
80.7 (71.3; 91.3) 88.9 (79.0; 100)
81.0 (69.9; 93.9) 84.7 (75.4; 95.2)
85.9 (77.6; 95.2) 90.9 (75.4; 100) 100
66.2 (47.4; 92.5)
95.0 (85.9; 100) 81.0 (72.6; 90.3)
97.8 (93.7; 100) 71.8 (60.5; 85.2)
64.9 (41.7; 100) 75.8 (63.2; 91.0) 94.3 (88.2; 100)
87.7 (78.0; 98.5)
61.7 (39.8; 95.6)
PFS: progression-free survival; OS: overall survival; CI: confidence interval; DEL: double expressor lymphomas; DH/TH: double-hit/triple-hit; CNS: central nervous system. *Log- rank test P-value; **Excluding 7 not-assessed patients; ***Excluding 53 not-assessed patients.
Results
Patients’ characteristics and treatment
A total of 122 patients affected by DEL were consecutive- ly treated with DA-EPOCH-R between November 2015 and March 2020. Patients’ characteristics are summarized in Table 1. The median age was 59 years (range, 24-79 years), and 62% were male.
MYC and BCL2 rearrangements by FISH were evaluated in all cases. BCL6 rearrangement could be done for 95 out of 122 patients (78%). According to IHC and FISH testing, the study population was divided into three subgroups: i) DEL only without any rearrangements (n=81, 66%); ii) DEL single-hit (DEL-SH) with either MYC or BCL2 rearrangement (n=9 MYC, n=13 BCL2); and iii) high-grade lymphomas (double-hit/triple-hit [DH/TH]) (n=10 MYC/BCL2, n=3 MYC/BCL6, n=6 MYC/BCL2/BCL6). The COO assignment according to Hans algorithm was ana- lyzed in 115 of 122 patients (94%) of whom 55 (45%) were GCB and 60 (49%) non-GCB.
Ninety-five (78%) patients had an advanced stage and 67 (55%) presented an IPI score of 3-5. Moreover, the number of patients with limited disease was low (n=27) with only four cases with stage I (all these cases present- ed with bulky extranodal disease) (Online Supplementary Table S1).
The median number of chemotherapy cycles was 6 (range, 1-6 cycles). Due to the aggressive clinical presen- tation requiring urgent treatment, 19 (15%) patients received the first cycle of R-CHOP while waiting for complete FISH analyses. Response assessment following DA-EPOCH-R treatment was feasible in 117 patients: of these 84 (72%) and 16 (14%) achieved a complete or par- tial remission, respectively. Seventeen patients (14%) showed progressive disease. Five patients were not evalu- able for a response after DA-EPOCH-R for toxicity (n=1, death of pneumonia), de-escalation therapy (n=2), consol- idation with high-dose therapy before the sixth cycle (n=2). Overall, 22 of 122 (18%) patients (n=12 DE, n=3 SH-BCL2, n=1 SH-MYC, n=6 DH/TH) underwent autol- ogous stem cell transplantation, in clinical remission, dur- ing treatment (n=2) and as consolidation after six cycles of DA-EPOCH-R (n=20) (Online Supplementary Table S2).
With the exclusion of one patient who died of pneumo- nia, other adverse events were manageable. We observed febrile neutropenia in 16 of 122 (13%) and infections requir- ing hospital admission (n=6 pneumonia, n=1 sepsis) in seven patients (6%).
Survival outcome
After a median follow-up of 24 months (interquartile range [IQR], 14-38 months), 110 patients were alive and 22
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