Data from a real-world analysis demonstrated the efficacy and safety of CAR T-cell therapy in primary mediastinal B-cell lymphoma.
Findings from a real-world study demonstrated that CD19-directed CAR T-cell therapy produced favorable outcomes across age subgroups in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBCL), irrespective of the CAR T-cell product utilized.1
Data presented at the
Notably, PFS (P = .2) and OS (P = .7) outcomes were consistent among patients treated with axicabtagene ciloleucel (axi-cel; Yescarta), lisocabtagene maraleucel (liso-cel; Breyanzi), and tisagenlecleucel (Kymriah). PFS (P = .4) and OS (P = .6) outcomes were also similar between age groups when comparing patients between 18 and 30 years of age, those between 30 and 45 years of age, and patients 45 to 77 years of age.
“This [was] the largest real-world study of CAR T-cell therapy in PMBCL to date,” lead study author Remy Dulery, MD, PhD, said in a presentation of the data. “Overall, our findings support the broad use of anti-CD19 CAR T-cell therapy in relapsed/refractory PMBCL, and [they] highlight the importance of disease control prior to [CAR T-cell therapy] infusion.”
Dulery is chief of the BMT and Cellular Therapy Unit at Saint Antoine Hospital and Sorbonne University in Paris, France.
PMBCL represented a distinct subtype within the LBCL realm, highlighted by a unique biological profile and a prevalence in younger adult patients. Although efficacy signals have been suggested in subgroups analyses of clinical trials evaluating CAR T-cell therapy in patients with non-Hodgkin lymphomas, outcomes for patients with rarer LBCL histologies such as PMBCL have not been well characterized.2
Thus, investigators sought to evaluate outcomes with CAR T-cell therapy in patients with relapsed/refractory PMBCL.1 Investigators used the EBMT Registry to identify patients at least 18 years of age with PMBCL who underwent CD19-directed CAR T-cell therapy between 2018 and 2025. Patients with secondary mediastinal involvement from other diffuse LBCL subtypes and those who underwent allogeneic hematopoietic stem cell transplant (HSCT) prior to CAR T-cell therapy were excluded from the analysis.
The primary end point of the study was 2-year PFS rate. Secondary end points included OS rate, relapse incidence, and non-relapse mortality (NRM) rate at 1 and 2 years; outcomes by prognostic factors such as CAR T-cell product and age; and the effect of pre– and post–CAR T-cell therapy strategies.
Among all patients included in the analysis (n = 284), the median age was 35 years (IQR, 29-43; range, 18-77). Half of patients were between the 30 and 45 years of age; 30% were between 18 and 30 years of age, and 21% were 45 to 77 years of age. Fifty-five percent of patients were female, and 45% of patients had a duration of diagnosis to treatment of less than 12 months. Number of prior lines of therapy included 1 (28%), 2 (49%), 3 (21%), and 4 (2.8%). Ten percent of patients underwent prior autologous HSCT. At the time of CAR T-cell therapy infusion, 6.0% of patients were in complete remission (CR), 27% were in partial remission (PR), and 67% had relapsed/refractory/progressive disease.
CAR T-cell therapy was administered to 45% of patients between 2018 and 2022, and the remainder were treated between 2022 and 2024.Hematopoietic cell transplantation–comorbidity index scores included 0 (69%), 1 to 2 (12%), and 3 or higher (20%). Patients had a baseline ECOG performance status of 0 (66%), 1 (30%), or 2 or higher (3.4%).
The 1- and 2-year NRM rates were 2.4% and 5.3%, respectively, among evaluable patients (n = 250). At 2 years, relapse was reported in 36.3% of patients. NRM outcomes and relapsed incidence did not vary among age subgroups.
Findings from a multivariate analysis also showed that patients with relapsed/refractory/progressive disease at the time of CAR T-cell therapy infusion had worse PFS outcomes (HR, 2.53; 95% CI, 1.42-4.50; P = .002) and a higher relapse incidence (HR, 2.47; 95% CI, 1.36-4.49; P = .003) compared with patients in CR or PR.
Patients with an ECOG performance status of 1 or higher were also associated with worsened OS outcomes compared with those who had an ECOG performance status of 0 (HR, 1.87; 95% CI, 1.04-3.33; P = .035).
Dulery explained that data collection is ongoing for the real-world study, and investigators will further analyze exposures to other treatment modalities prior to and after CAR T-cell therapy, such as first-line chemotherapy backbone, immune checkpoint inhibitors, bispecific antibodies, HSCT, and radiotherapy. Another subgroup analysis will explore outcomes based on number of prior lines of therapy.
Safety analyses will also be conducted to explore the incidences of cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, cytopenias, and infections.
Disclosures: Dulery reported receiving grant and research support from Ligue Nationale contre le Cancer and the Philippe Foundation, and receiving non-financial support from Kite and Gilead.
