Gemcitabine, Carboplatin, Dexamethasone, and Rituximab Versus High‐Dose Cytarabine‐Based Chemotherapy as Second‐Line Treatments for Relapsed or Refractory Diffuse Large B‐Cell Lymphoma

The optimal second-line chemotherapy regimen for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains uncertain. We retrospectively compared efficacy and safety between gemcitabine, carboplatin, dexamethasone, and rituximab (GCD-R) and cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) as second-line treatments for R/R DLBCL. We evaluated 68 R/R DLBCL patients receiving either GCD-R (n = 42) or CHASER (n = 26) as second-line treatment between 2004 and 2020. The primary endpoint was the complete response rate (CRR). Secondary endpoints included overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events. CRR (43% vs. 42%; p = 1.00) and ORR (60% vs. 50%; p = 0.46) were comparable between GCD-R and CHASER groups. Median OS (GCD-R 18.6 months, CHASER 11.2 months; p = 0.93) and median PFS (GCD-R 10.0 months, CHASER 4.6 months; p = 0.47) showed no significant differences between groups. Further, among patients who subsequently underwent autologous stem cell transplantation, OS was also comparable between groups (p = 0.44). However, febrile neutropenia was significantly less frequent with GCD-R (33%) than with CHASER (92%; p < 0.001). As GCD-R predominantly uses peripheral intravenous catheters, whereas CHASER frequently requires central venous access, catheter management was significantly simpler with GCD-R (p < 0.001). GCD-R demonstrated equivalent efficacy to CHASER with significantly reduced toxicity and improved patient management, supporting its use as an effective and well-tolerated salvage therapy for R/R DLBCL. GCD-R represents a feasible treatment option not only for elderly patients, but also for patients eligible for subsequent stem cell transplantation.