Comparative Analysis of Lymphodepletion Regimens in CART-19 Treatment for Relapsed/Refractory Diffuse Large B Cell...

Patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) undergoing chimeric antigen receptor T cell therapy targeting CD19 (CART-19) receive preinfusion lymphodepletion (LD), most commonly with fludarabine/cyclophosphamide (flu/cy). During the fludarabine shortage, bendamustine was used as an alternative. There are only limited data on how outcomes with flu/cy and bendamustine LD compare. We aimed to compare outcomes and toxicity profiles in r/r DLBCL patients lymphodepleted with flu/cy or bendamustine prior to CART-19 therapy.We conducted a retrospective single-center study comparing DLBCL patients who received axicabtagene ciloleucel (axi-cel; 74.4%) or lisocabtagene maraleucel (liso-cel; 25.6%) following flu/cy or bendamustine LD. A propensity score-matched data set was created to balance baseline covariates between the LD groups (45 patients per LD group). Covariates addressed included age, stage, bridging therapy, number of prior therapies, CART-19 product, and pre-LD C-reactive protein (CRP) and lactate dehydrogenase (LDH). Outcomes, including response rates, overall survival (OS), progression-free survival (PFS), cytokine release syndrome (CRS), immune effector cell neurotoxicity syndrome (ICANS), and hematologic toxicities, were evaluated.The 3-month overall and complete response rates (ORR; CR) were similar in the flu/cy (64.4% and 60%) and bendamustine groups (64.4% and 51.1%; ORR: P = 1; CR: P = .40). At 6 months, no differences in PFS (flu/cy 62.2% vs bendamustine 58.2%; P = .37) or OS (flu/cy 86.7% vs bendamustine 79.9%; P = .83) were noted. Incidences of CRS and ICANS were comparable in the flu/cy (CRS, 79.1%; ICANS, 42.2%) and bendamustine cohorts (CRS, 71.1%; ICANS 28.9%; all P > .05). However, the median time to peak CRS (3 vs 5 days; P = .002) and ICANS (6 vs 9 days; P = .034) occurred earlier in the flu/cy cohort. The flu/cy cohort also had lower median absolute neutrophil, platelet and hemoglobin nadirs (all P ≤ .001). Moreover, flu/cy was associated with higher rates of severe (G ≥ 3) neutropenia (100% vs 73%; P < .001), anemia (54.5% vs 24.4%; P = .012), and thrombocytopenia (57.5% vs 29.7%; P = .019). Within the limitations of the size of our study and its retrospective nature, flu/cy and bendamustine LD resulted in similar ORR, PFS and OS; however, bendamustine had less hematologic toxicity. Bendamustine can be a viable alternative LD agent for CART-19 therapy for DLBCL, especially in patients with a compromised performance status.