Efficacy of Lisocabtagene Maraleucel for Relapsed or Refractory Aggressive B Cell Lymphoma in Our Hospital
Authors: Kaji Daisuke , Watanabe Otoya , Yamaguchi Kyosuke , Kageyama Kosei , Taya Yuki , Nishida Aya , Takagi Shinsuke , Yamamoto Hisashi , Ishiwata Kazuya , Asano-Mori Yuki , Wake Atsushi , Uchida Naoyuki , Yamamoto Go 
Published: December 2023

[Background] Although the standard treatment for relapsed or refractory large B-cell lymphoma (LBCL) is high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT), the prognosis of relapsed or refractory LBCL is poor. The chimeric antigen receptor (CAR) T-cell therapy showed efficacy against relapsed or refractory LBCL. However, little real-world data on lisocabtagene maraleucel (liso-cel) were reported. Therefore, we report our data on liso-cel for relapsed or refractory LBCL in our institution.

[Methods] We retrospectively analyzed clinical characteristics of patients who underwent leukapheresis to manufacture liso-cel between August 2021 and March 2023 at Toranomon Hospital. Overall survival (OS), progression-free survival (PFS), and duration of response (DOR) were calculated using the Kaplan-Meier method. OS was defined as the time from infusion of liso-cel to the date of death or last follow-up. PFS was defined as the time from infusion of liso-cel to progression of disease or death. DOR was defined as the time from first complete response or partial response to disease progression or death. The Cox proportional hazards model was used to determine the significance of multiple variables.

[Results] Leukapheresis for the manufacture of liso-cel was performed in 25 cases. Of these 25 cases, liso-cel could not be manufactured in only one patient, and the other 24 patients received liso-cel infusion. Of the 24 patients who received liso-cel, 14 were men and the median age was 64.5 years (range, 29-78). Twenty-one patients had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1; the other 3 had a PS of 2. The other clinical characteristics were as follows: Stage III/IV in 21 (87.5%); Bulky mass in 6 (25%); extranodal involvement &gt; 1 in 9 (38%); international prognostic index (IPI) &gt; 2 in 13 (54%); and elevated LDH in 11 (46％). Histological diagnoses were diffuse large B-cell lymphoma (n=13), transformed follicular lymphoma (n=6), primary mediastinal large B-cell lymphoma (n=3), and high-grade B-cell lymphoma (n=2), respectively. Secondary central nervous system (CNS) involvement was detected in 4 cases. The number of patients with primary refractory disease or relapse within 12 months after first-line chemotherapy is 10 (42%) and 10 (42%), respectively. Since 10 patients with primary refractory disease required immediate chemotherapy until leukapheresis was performed, liso-cel was used as a third-line or later in all cases. Patients had received a median of 4 (range, 2-9) previous lines of chemotherapy. Six patients (25%) had received a previous autologous HSCT, and two (8%) had received a previous allogeneic HSCT, respectively. The median time from leukapheresis to liso-cel arrival at our institution was 42 (range, 37-45) days. Bridging chemotherapy after leukapheresis was performed in all cases, with polatuzumab vedotin plus bendamustine and rituximab (Pola-BR) being the most common with 13 cases (54%). Eight cases (33%) had achieved complete response (CR), and 8 cases (33%) had achieved partial response (PR) before lymphodepleting chemotherapy. The median follow-up of survivors was 7.7 months (range, 2.5-14.5). The median OS, PFS, and DOR were 11.5 months (95% confidence interval [CI]: 8.9 to not applicable, NA), 8.5 months (95% CI: 2.1 to NA), and 8.9 months (95% CI: 3.3 to NA), respectively. The overall response rate was 71%, with 54% achieving CR. Cytokine release syndrome (CRS) and neurological events (NEs) occurred in 21 (88%) and 2 patients (8%); grade 3 or worse CRS and NEs occurred in 1 (4%) and 2 patients (8%). Grade 3 or worse neutropenia, anemia, and thrombocytopenia were occurred in 23 (96%), 14 (50%), and 17 cases (71%), respectively. Prolonged Grade 3 or worse neutropenia was seen in 12 cases (50%) at 28 days after liso-cel infusion. No treatment-related death was not observed. Six patients died, and the causes of death were LBCL (n=3), pneumonia (n=2), and COVID-19 (n=1). In the multivariate analysis, independent risk factors for PFS were PS of 2 (hazard ratio [HR], 56.39; 95% CI, 8.31 to 382.7; p&lt;0.001) and disease status (stable disease/progressive disease) before lymphodepleting chemotherapy (HR, 6.14; 95% CI, 1.07 to 35.06; p=0.04).

[Conclusion] In our cohort, liso-cel has shown high response in relapsed or refractory LBCL. Disease status before lymphodepleting chemotherapy is significant for better prognosis.