Axicabtagene Ciloleucel Demonstrates Higher ORR in Japanese Patients With Relapsed or Refractory DLBCL

In the J201 bridging study, the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel demonstrated efficacy in Japanese patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The overall remission rate (ORR) was 86.7% (95% CI: 59.5%–98.3%), which was even higher than it was in the pivotal ZUMA-1 study (82%), which did not include any Japanese patients.

Non-Hodgkin lymphoma (NHL) is the tenth most common type of cancer in Japan and DLBCL is the most common subtype, according to Koji Kato, Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan, and colleagues.

“Although the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has improved the prognosis of DLBCL patients, 30%-50% of them are not cured by this treatment,” Dr Kato et al wrote.

J201 is a phase 2, multicenter, open-label, single-arm trial which aimed to confirm the efficacy and safety of axicabtagene ciloleucel in Japanese patients with DLBCL.

Of the 16 subjects who received a single infusion of axicabtagene ciloleucel (2.0× 10⁶ cells/kg), 14 (87.5%) were diagnosed with DLBCL per investigator assessment. However, efficacy was evaluable in 15. Seven (43.8%) patients had stage IV disease. At baseline, 13 (81.3%) patients were CD19 positive and.1 patient was negative by immunohistochemistry; for 2 patients, data were missing, the authors said. Twelve (75.0%) patients had received ≥3 prior therapies; 10 (62.5%) patients were refractory to second- or subsequent-line therapy; and 6 (37.5%) relapsed after autologous stem cell transplant (ASCT) within a year.

By the data cut-off of October 23, 2019, the objective response rate (ORR) was 86.7% (95% CI, 59.5%-98.3%) in 15 the efficacy-evaluable patients. Complete response (CR) was observed in 4 (26.7%) patients, and partial response (PR) was observed in 9 (60%). Two patients died due to disease progression.

No dose-limiting toxicities were observed. All 16 patients experienced a grade ≥3 treatment-emergent adverse events (TEAE), including neutropenia (81.3%), lymphopenia (81.3%) and thrombocytopenia (62.5%). Cytokine release syndrome (CRS) occurred in 13 (81.3%) patients (12 cases of grade 1 or 2, and 1 case of grade 4). No neurologic events occurred. No treatment-related death was observed.

Source:
Kato K, Makita S, Goto H, et al. Phase 2 study of axicabtagene ciloleucel in Japanese patients with relapsed or refractory large B-cell lymphoma. Int J Clin Oncol. 2022;27(1):213-223.