
Patients with CAR-19 progressing large B-cell lymphoma (LBCL) had durable remissions and long-term survival on treatment with firicabtagene autoleucel, according to findings from a single-center, dose-escalation phase 1 trial (NCT04088890) presented at the American Society of Hematology Annual Meeting and Exposition by Anne Marijn Kramer, MD, PhD, of Cancer Center Amsterdam, Department of Hematology, Amsterdam UMC, Netherlands.
“Antigen loss or down regulation following CAR19 therapy is associated with 30%-50% of patients with lymphoma progression. Clearly having additional safe and effective CAR-T therapies beyond CAR19 is a promising strategy and our CAR22 results showing 53% CR and durable responses proves patient benefit,” study co-investigator David M. Miklos MD, PhD, of Stanford University, told Blood Cancers Today.
At a median follow-up of 6.7 months (range, 20.2-56.8 months) in 38 patients with LBCL who received 1 and 3 million CAR22-positive T cells/kg via IV infusion, the overall response rate was 68% with complete response rate of 53%. The median duration of response observed was 23.2 months (95% CI, 1.9 to not estimable).
Regarding survival, the median progression-free survival (PFS) was 3.0 months (95% CI, 1.6 to not estimable), and the median overall survival (OS) was 25.7 months (95% CI, 9.18 to not estimable). Kramer et al also estimated 3-year PFS and OS rate to be 30% (95% CI, 17%-53%) and 47% (95% CI, 32%-70%), respectively.
No cytokine release syndrome or ICANS was observed at the recommended phase 2 dose of firicabtagene autoleucel during the study. Further, investigators observed 27 PFS events, of which 22 were a result of lymphoma progression following CAR22 therapy. At a median of 30 months (range, 8-39 months) post infusion, four patients were diagnosed with secondary malignancies, all of which were treatment related myeloid neoplasms. Notably, these patients had undergone a median of four prior lines of therapy.
Long-term complications including non-relapse mortality (NRM), prolonged cytopenia, and infections were evaluated during the study. There were six NRM events, which occurred within one year after CAR22 therapy for three patients, between and and two years post-CAR22 for one patient, and after two years for two patients. Moreover, one case of NRM was related to secondary infection while two patients experienced treatment-unrelated cardiac events, one died due to unknown causes after being lost to follow-up, and two patients had disease progression or died due to progression of tMDS/AML.
Investigators observed a 45% 3-year cumulative incidence of death after disease progression and a 3-year risk of non-relapse mortality 14%.
Of the patients who responded to firicabtagene autoleucel treatment, two of 14 had greater than or equal to grade 2 cytopenia at the 1-year timepoint, and 0 of 10 patients had cytopenia at the 2-year milestone. Four of 18 patients developed infections and were hospitalized six months after infusion or later. 10 of 18 patients required IV immunoglobulin treatment three months after infusion or later.
According to Kramer et al, late progression or lymphoma-specific death was uncommon in the study population. These findings signal that firicabtagene autoleucel may have curative potential in CAR19-progressing LBCL. The safety profile for firicabtagene autoleucel was manageable, albeit in a heavily pretreated population with high risk for tMDS/AML. Lifelong follow-up is recommended based on the findings. Investigators also noted that it will be important to explore this therapy in earlier treatment settings.
“At Stanford, we are extending CAR22 use to patients with MCL and FL in Stanford-sponsored investigator-initiated trials led by Dr. Matthew J. Frank,” said Dr. Miklos.
Reference:
Kramer A, Baird J, Srinagesh H, et al. CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: Continued durable remissions at 3-year follow-up. Presented at American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024. San Diego, CA. Abstract 69.