Frederick L. Locke, MD
The combination of the anti‑CD19 chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) and the PD-L1 inhibitor atezolizumab (Tecentriq) was highly active with a manageable safety profile in patients with refractory diffuse large B-cell lymphoma (DLBCL) enrolled in the phase I/II ZUMA-6 trial.1
Axi-cel–related AEs occurred in all 9 patients and 4 patients experienced atezolizumab-related AEs. Overall, 8 patients experienced grade 3/4 AEs. There were 3 grade 3 and 4 grade 4 AEs related to axi-cel, and 1 grade 4 AE related to atezolizumab.
Across the study population, grade 3/4 treatment-emergent AEs occurring in at least 3 patients included anemia (n = 7), encephalopathy (n = 5), neutropenia (n = 4), hyponatremia (n = 3), decreased lymphocyte count (n = 3), decreased neutrophil count (n = 3), pyrexia (n = 3), and thrombocytopenia (n = 3). Additionally, grade 3 hypophosphatemia, hypoxia, blood bilirubin increase, and lung infection occurred in 2 patients each.
Combining axi-cel with atezolizumab did not result in an increased use of tocilizumab or steroids. One patient had a DLT related to cytopenias that lasted for more than 30 days. There were no patient deaths.
Moving forward, Locke said, “The next step will be to expand it into a phase II trial. So, we really want to find the safe schedule to combine these 2 therapies. Once we’ve settled on a dosing schedule, we will expand with another 22 patients and see if it improves the efficacy as compared to [the efficacy with axi-cel alone] in the DLBCL patients who were treated on the ZUMA-1 trial.”
- Locke FL, JR Westin JR, Miklos DB, et al. Phase 1 results from ZUMA‑6: axicabtagene ciloleucel (axi-cel; KTE-C19) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta. Abstract 2826.
- Neelapu SS, Locke FL, Bartlett NL, et al. Long-Term Follow-up ZUMA-1: A Pivotal Trial of Axicabtagene Ciloleucel (Axi-Cel; KTE-C19) in Patients with Refractory Aggressive Non-Hodgkin Lymphoma (NHL). Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta. Abstract 578.
... to read the full story