Analysis of Patient Characteristics and Treatment Progression Patterns in R/R DLBCL Patients Prior to CAR T-Cell Therapy in EU4+UK Countries

Introduction: CAR T-cell therapies have changed the therapeutic landscape for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). The aim of this study was to identify differences in patient profiles and treatment patterns between two patient groups in the R/R DLBCL segment: one patient group receiving CAR T-cell therapy and one receiving systemic therapy. Further, we wanted to understand the pre-CAR T-cell progression/relapse characteristics that drove the patients to receive CAR T-cell treatment.

Methods: 153 hemato-oncologists across France, Germany, Italy, Spain, and UK participated in a retrospective longitudinal study reporting R/R DLBCL patients treated between January and June 2022. Data recorded for each patient included diagnosis information, details about the ongoing therapy but also the previous drug-treatment therapies, and mutations/chromosomal abnormalities status.

Results: Data of 457 R/R DLBCL patients were reported and used to perform this research. At the time of data collection 148 patients were receiving CAR T-cell therapy and 309 patients were receiving systemic therapy. All the patients were in their 3^rd line or 4^th line at that point in time. Moreover, the previous line of drug therapy each patient received was collected as well. For those under CAR T-cell therapy, both lymphodepleting regimen and infusion were considered as part of the current treatment.

53% of CAR T-cell treated patients were in the age range of 51-65 years old, while only 17% of the systemic therapy population fell under this age group. The main age range in the systemic therapy group was 65 years or above (75%), while only 21% of CAR T-cell treated group were in this age range.

95% of the patients being treated with a CAR T-cell therapy had a 'fit' status according to their treater, while only 41% of systemic therapy-receiving patients were considered fit.

The following features were observed in the CAR T-cell treated population (148 patients):

• 76% had an ECOG status 0 or 1.

• 45% did not present any comorbidities.

• 39% (58 out of 148) received a stem cell transplant (SCT). 71% (41 out of the 58) of these received it in their second line, with majority (95%, 39 out of 41) of them being autologous.

• 57% of the patients started CAR T-cell therapy between 1 and 3 years after the initial diagnosis.

• Focusing on the time between the start of prior treatment and the start of CAR T-cell therapy, 45% of the patients fell under the range of 0 to 6 months, 33% in the 6 to 12 months range, 11% in the 12 to 18 months range, 5% in the 18 to 24 months range and 6% within more than 2 years.

• Among the reasons for stopping the treatment prior to CAR T-cell therapy, 61% was due to course completed, 30% due to progression, 10% due to stable disease, 9% due to patient's choice, 5% due to COVID pandemic, 2% due to side effects and 1% due to poor performance status (reasons can be multiple for each patient).

• Focusing on the relapse or progression of the treatment given prior to the CAR T-cell therapy 26% of the patients progressed during that prior treatment, 21% were reported as not having presented a relapse, 14% progressed within less than 3 months after ending the prior treatment, 11% did it within the 3 to 6 months range, 14% within the 6 to 12 months range and 7% progressed more than 12 months after ending their prior treatment (8% information not available).

Conclusions: In EU4+UK R/R DLBCL patients who received CAR T-cell therapy presented with a better fitness status, younger age profile, lower ECOG status, and less comorbidities compared to the population who received systemic therapy. SCT was considered as a treatment option prior to CAR T-cell therapy as it was performed in 39% of the cases. Close to 60% of the patients received the CAR T-cell therapy within the 1 to 3 years after the initial diagnosis. In almost 80% of the patients the elapsed time between the start of the prior therapy and the CAR T-cell therapy was less than a year. In line with these results, it was also observed that 51% of the patients presented a progression within the 6 months after ending the prior therapy. These results indicate a very aggressive disease, potentially suggesting the need to use CAR T-cell therapies in this population. Further research would be required to understand the pool of 21% patients reported as "not progressed or relapsed" after their prior treatment.

No relevant conflicts of interest to declare.