Bendamustine as Lymphodepleting Chemotherapy Prior to Axicabtagene Ciloleucel for the Treatment of Relapsed / Refractory Large B-Cell Lymphoma

Dr Alaa Ali presents an analysis from the CIBMTR registry, comparing the real-world safety and effectiveness of single-agent bendamustine versus standard fludarabine/cyclophosphamide (Flu/Cy) as lymphodepleting chemotherapy (LDC) before axicabtagene ciloleucel (axi-cel) for the treatment of relapsed/refractory large B-cell lymphoma. 

Over 650 patients treated between 2022 and 2023 were included, with 20% receiving bendamustine and 80% receiving Flu/Cy. Propensity score weighting and multivariate analysis were used to compare the two groups. The analysis revealed that Flu/Cy was associated with significantly higher complete remission rates and improved progression-free survival. However, bendamustine exhibited a significantly reduced toxicity profile. Key findings included lower rates of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and prolonged thrombocytopenia in the bendamustine group. Additionally, there was a notable reduction in the use of tocilizumab and steroids in the bendamustine group, indicating a generally milder toxicity course. The onset of toxicity was also delayed in the bendamustine group, with CRS developing in 6 days, compared to 5 days in the Flu/Cy group. ICANS took 8 days to manifest in the bendamustine group versus 6 days in the Flu/Cy group. 

Although bendamustine did not outperform Flu/Cy in terms of efficacy, it was considered a reasonable alternative, especially during drug shortages or in high-risk patients, such as the elderly or those with comorbidities, as it reduces toxicity.