The Interim Results Of The Significance Of Upfront High-Dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplantation For Iv Stage And High-Intermediate/High Risk Groups Of Diffuse Large B-Cell Lymphoma With Complete Response After Induction Chemotherapy

Context Approximately 30% of patients (pts) with IPI≥2 diffuse large B-cell lymphoma (DLBCL) have relapsed after the frontline regimens. High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in the first remission can be an effective option to decrease the relapse rate in these patients. Objectives To determine the significance of the upfront HDCT with auto-HSCT for IV stage DLBCL pts with unfavorable prognosis and complete response (CR) after induction. Design and Interventions 112 pts: DLBCL NOS, age 18-65, stage IV, IPI≥2, CR/PR after x6 CHOP/EPOCH/H-CVAD+R from 2010 to 2019 at NMRC of Oncology named after N.N.Petrov of MoH of Russia were retrospectively analyzed. Group 1 (G1) includes pts with upfront HDCT followed by auto-HSCT (n=38). Group 2 (G2): follow-up pts (n=74). Median observation time (mon): G1–47.3 (6-82), G2–53.4 (3-130). Outcome measures Complete response (CR), 2-yr relapse rate (RR), 2-yr progression-free survival (PFS). Results CR after induction was achieved in 61% (23/38) pts in G1. After HDCT with auto-HSCT, the CR rate increased to 97% (37/38). McNemar=11.27 (p≤0.001), Yates=10.42 (p=0.002). CR rate in G2: 79.7% (59/74). G1 had the 10% (4/38) 2-yr relapse rate (RR), G2–25.6% (19/74). Factors (Fisher's), increasing the 2-yr RR in CR pts (G1-37 vs G2-59) were: C-myc≥40% (RR=G1–7.1% (1/14) vs 46.1% (6/13), p=0.007), extra>1 site with lung involvement (RR=G1–0% (0/8) vs 50% (5/10), p=0.0359), DEL (RR=G1–6.2% (1/16) vs 62.5% (5/8), p=0.0069). The binominal logistic regression (BLR) was used to define prognostic factors on 2-yr PFS in CR after induction pts. BLR model included the presence/absence of upfront HDCT with auto-HSCT (23/83), tumor-infiltrating CD3(+) T-cells (TILs)≥20% (27/65), >1 extra-nodal sites (59/83), DEL (21/62), B-symptoms (40/83), PLT≥320x109/l (44/83) and Ki67 as a covariate. The BLR model predictive accuracy: 88.3% (95% CI 74.9%–96.1%), sensitivity: 70% (95% CI 34.8%–93.3%), pos likelihood ratio (LR): 11.5 (95% CI 2.84–46.9), neg LR–0.32 (95% CI 0.12–0.83); AUC=0.915. Factors which increased the chance of 2-yr PFS were upfront HDCT with auto-HSCT (p=0.046, OR=14.3 (1.05– 195.26)); CD3(+) TILs≥20% (p=0.022, OR=77.3 (1.89–3153.25)). Factors which decreased the chance of 2-yr PFS were extra>1(p=0.047, OR=0.02 (4.4e–4–0.95)); DEL (p=0.026, OR=0.02(7.38e–4–0.91)). Conclusions CR rate significantly increased in DLBCL NOS pts with stage IV, IPI ≥2 treated by upfront HDCT with auto-HSCT. Two-year RR was significantly higher if DLBCL NOS pts with stage IV, IPI≥2 had extra>1 site with lung involvement or c-myc≥40% or DEL and didn't proceed to upfront HDCT with auto-HSCT. Upfront HDCT with auto-HSCT and CD3(+) TILs≥20% were favorable for 2-yr PFS. Extra>1 and DEL were unfavorable for 2-yr PFS.