High CR rates for novel CAR T-cell therapy in follicular lymphoma and DLBCL
The investigational CAR T-cell therapy AZD0486 was associated with high complete response (CR) rates in patients with relapsed or refractory follicular lymphoma or patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), supporting further exploration of the drug.
Follicular lymphoma
“The investigational agent AZD0486 is a CD19 and CD3 bispecific T-cell engager,” said Dr Jing-Zhou Hou (University of Pittsburgh Medical Center, PA, USA) [1]. It was evaluated in a phase 1 study among patients with relapsed or refractory follicular lymphoma. The 56 participants had CD19-positive disease and had received at least 2 prior lines of therapy. “Of the 56 included participants, 41 received the target dose of at least 2.4 mg,” added Dr Hou.
Among the 41 participants who had received the target dose of AZD0486, the overall response rate was 95%, and the CR rate was 85%. The median duration of response had not been reached after 8.4 months of follow-up. Furthermore, the estimated 12-month progression-free survival (PFS) rate was 75–79%.
“No participants had discontinued therapy due to treatment-related adverse events [AEs],” expressed Dr Hou. Cytokine release syndrome (CRS), anaemia, decreased lymphocyte count, and nausea were frequently reported side effects. “In the double step-up group [n=38], we only saw grade 1 CRS [n=19] and grade 1 immune effector cell-associated neurotoxicity syndrome [ICANS; n=1].”
“AZD0486 showed a high CR rate and was well tolerated among heavily pre-treated patients with follicular lymphoma,” concluded Dr Hou. “Additional studies are ongoing to further assess the value of AZD0486 in this population.”
Diffuse large B-cell lymphoma
Another cohort within the same study included 58 participants with relapsed or refractory DLBCL [2]. “Over 50% of the participants had received 4 or more prior lines of therapy, 34% was primary refractory, and 59% had already received CD19-directed CAR T therapy,” emphasised Dr Sameh Gaballa (Lee Moffitt Cancer Center, FL, USA), to illustrate that the cohort comprised a heavily pre-treated population of patients with DLBCL.
The overall response rates were 39% in the 2.4 mg group, 47% in the 7.2 mg group, and 50% in the 15 mg group. The corresponding CR rates were 22%, 42%, and 39%. In CAR T-naïve patients who received the target dose of 7.2 mg or 15 mg, the CR rates were 80% and 38%, respectively. The matching CR rates for CAR T-exposed participants were 29% and 40%. After a median follow-up of 5 months, no participants who had achieved a CR had progressed.
The most common grade 3 or higher treatment-related AEs were neutropenia (19%), lymphopenia (9%), anaemia (5%), and ICANS (5%). “There were no treatment-related AEs resulting in discontinuation and no treatment-related deaths,” added Dr Gaballa.
“AZD0486 demonstrated promising clinical activity in these heavily pre-treated patients with DLBCL,” concluded Dr Gaballa. “The study will continue to evaluate AZD0486 in patients with relapsed or refractory non-Hodgkin lymphoma.”
- Hou J-Z, et al. Escalating doses of AZD0486, a novel CD19xCD3 T-cell engager, result in high complete remissions with rapid clearance of minimal residual disease in patients with relapsed/refractory follicular lymphoma. Abstract 341, 66th ASH Annual Meeting, 7–10 December 2024, San Diego, CA, USA.
- Gaballa S, et al. Evaluation of AZD0486, a novel CD19xCD3 T-cell engager, in relapsed/refractory diffuse large B-cell lymphoma in an ongoing first-in-human phase 1 study: high complete responses seen in CAR T-naïve and CAR T-exposed patients. Abstract 868, 66th ASH Annual Meeting, 7–10 December 2024, San Diego, CA, USA.