December 11, 2023
By Dibash Kumar Das, PhD
In a recent multicenter retrospective study conducted by the Cell Therapy Consortium, clinicians assessed the real-world application of lisocabtagene maraleucel (liso-cel), an autologous CD19-directed CAR T-cell therapy approved for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The study, presented at the 65th ASH Annual Meeting and Exposition, aimed to provide insights into the safety and efficacy of liso-cel in standard clinical practice, extending beyond the controlled environment of clinical trials (Abstract 617).
The study included patients aged 18 years and above with LBCL who received commercial liso-cel infusion between February 2021 (time of FDA approval) and June 2023 at seven academic U.S. medical centers. The researchers identified patients from the Cell Therapy Consortium registry and conducted a retrospective analysis. Patient and treatment characteristics were summarized descriptively, and survival outcomes were analyzed using the Kaplan Meier method. The grading of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) followed ASTCT consensus criteria, and tumor response was assessed according to Lugano criteria.
As of June 10, 2023, a total of 101 patients underwent liso-cel infusion. The patient demographics revealed a median age at apheresis of 71 years with 35 percent of patients aged 75 years or older. The majority were male (60%), and 16 percent had an ECOG PS of ≥2 at apheresis. Notably, 30 percent of patients would have been ineligible for the TRANSCEND clinical trial due to comorbidities.
The study encompassed diverse histological subtypes, with 86 percent having DLBCL, 7 percent HGBL, 5 percent TFL, and 2 percent PMBCL. Baseline comorbidities included diabetes (18%), Stage IV chronic kidney disease (5%), and other conditions. The median number of prior therapies was three, with 16 percent undergoing prior autologous stem cell transplant.
The analysis reported any Grade CRS in 49 percent of patients (3% Grade ≥3) and any Grade ICANS in 26 percent (10% Grade ≥3). Tocilizumab was administered in 31 percent, and 31 percent received steroids for toxicity management. The 6-month incidence of non-relapse mortality was 8 percent. Response rates to bridging therapy and liso-cel infusion were promising, with an overall response rate (ORR) of 81 percent at Day 30 and 63 percent at day 90.
To gain additional insights into the study, Oncology Times connected with study author Peter A. Riedell, MD, Associate Professor of Medicine at the David and Etta Jonas Center for Cellular Therapy at UChicago Medicine. He Riedell specializes in the management of lymphomas and chronic lymphocytic leukemia in adults, with a particular focus on leveraging chimeric antigen receptor (CAR) T-cell therapy for treating these disorders.
Oncology Times: How does the use of bridging therapy, such as polatuzumab-based treatment, chemoimmunotherapy, and radiation therapy, impact the outcomes of patients treated with liso-cel? What are the implications for debulking disease prior to CAR T-cell therapy?
Riedell: “In our analysis, 62 percent of subjects received bridging therapy prior to liso-cel infusion. Common bridging therapy regimens included polatuzumab-based treatment (41%), chemotherapy (24%), and radiation therapy (21%). Collectively, these bridging strategies elicited an overall response rate of 45 percent and a complete response rate of 17 percent. Prior reports by our group and others have demonstrated high response rates and durable remissions in patients treated with CAR T-cell therapy while in a CR. Therefore, the high CR rate seen in bridging therapy in our study likely bolstered outcomes in liso-cel recipients. These findings suggest that the successful use of bridging therapy to temporize and debulk disease may be a key factor in CAR T-cell efficacy.”
Oncology Times: What ongoing research efforts and follow-up studies are planned to further assess the long-term efficacy, safety, and durability of responses in patients receiving liso-cel in real-world settings? How might these findings inform future treatment guidelines and clinical decision-making for patients with relapsed/refractory LBCL?
Riedell: “The current data cut, as presented at the 2023 ASH meeting, included a median follow-up of 12.4 months. Therefore, longer follow-up will be needed to gain a better understanding of longitudinal efficacy and safety outcomes in recipients of liso-cel. Follow-up analyses of interest include multivariable logistic regression modeling to gain a better understanding of the impact of key co-variates on efficacy and safety outcomes. Furthermore, we plan to compare the results noted in this analysis to patients treated with axicabtagene ciloleucel or tisagenlecleucel during the same time frame to better understand patterns of CAR T-cell efficacy and safety, and gain insights into patient selection. Such data may help inform treatment guidelines and clinical decision-making.”
Dibash Kumar Das is a contributing writer.