In previous several studies it was confirmed that double expression of both c-myc and bcl-2 in Diffuse Large B-cell lymphoma patients (DLBCL) predict aggressive course. We suggest that it can be independent risk factor and early treatment intensification can provide potential benefit for this poor risk group.
To analyze data we used chi-square test for independence, odds ratio (OR), full analisys test. Progression free survival (PFS) were estimated by Kaplan-Meier method, comparison of PFS in experimental groups (long-rank test), multifactor analysis of PFS (multinomial logistic regression). Statistically significant difference if p < 0,05.
We analyzed 240 pts with DLBCL, from 18 to 85 y.o. (median age 56 y.o), who underwent treatment in National Medical Research center from 2008 to 2018. Seventy six (32%)-with early stage of disease (I,II) and 164 pts (68%)-advance stage (III,IV). Extranodal involvements were observed in 61 pts (25%) and B-symptoms in 109 (45%), GCB-subtype in 47% and non-GCB in 53% (Hans algorithm). DA-EPOCH-R, Hyper-CVAD-R as first line received 26 pts (11%) and up-front high-dose chemotherapy with AutoSCT received 17 pts (7%). 2-years PFS was 86% for all pts [95% CI 78-94]. PFS was significantly lower in pts with B-symptoms (38% vs 84%; RR 3,3 [95% CI 0,85 – 1,4], p < 0,05); advance stage (42% vs 89%; RR 3,0 [95% CI 1,7 – 2,1], p < 0,05); c-myc expression (45% vs 84%); RR 1,9 [95% CI 0,3 - 0,9 ], p < 0,05); bcl-2-expression (60% vs 83%) RR 1,6 [95% CI 1,2 – 1,9], p < 0,05); Ki-67 higher than 70% (59% vs 89%; RR 2,5 [95% CI 0,9 – 1,2], p < 0,05). Double-expressor lymphoma (DEL) (both c-myc and bcl-2) were observed in 33% (80 patients). Among patients with DEL, PFS were lower but not significantly different comparing with non-DEL (p = 0,03). These data were related to early treatment intensification in this subgroup (DA-EPOCH-R, Hyper-CVAD-R, up-front high-dose chemotherapy with AutoSCT). DEL subgroup was also associated with advance stage of the disease (III-IV 68% vs I-II 39%, p < 0,05), B-symptoms (69% vs 47%, p = 0,03) and Ki-67 higher than 70% (81% vs 71%, p > 0,05).
These data confirm more aggressive course of the disease in patients with DEL comparing with standard group and may suggest benefit for patients to undergo early-treatment intensification.
Clinical trial identification
Legal entity responsible for the study
Tatiana Semiglazova. MD.
Has not received any funding.
All authors have declared no conflicts of interest.