Swetha Kambhampati, MD, hematologist/oncologist, assistant professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the rationale for evaluating outcomes with brexucabtagene autoleucel (Tecartus; brexu-cel) in a subgroup anlaysis of patients with relapsed/refractory mantle cell lymphoma (MCL), and how prior data from the phase 3 ZUMA-2 study (NCT02601313) supported the inception of this trial.

Brexu-cel is currently the only FDA-approved CAR-T product for the treatment of patients with relapsed/refractory MCL, Kambhampati begins. 

The agent's approval in 2020 was based on findings from the pivotal ZUMA-2 trial

 which demonstrated that treatment with brexu-cel produced an overall response rate of 91%, including a complete response rate of 68% in patients who had received more than 2 prior lines of therapy. Notably, all patients enrolled in ZUMA-2 had been previously treated with BTK inhibitors, although the FDA indication for brexu-cel doesn't require patients to have received prior treatments, Kambhampati notes. Moreover, the estimated median duration of response with the agent was not reached after a median follow-up of 8.6 months.

Regarding safety, 18% and 37% of patients treated with brexu-cel experienced grade 3 or greater cytokine release syndrome (CRS) and neurologic toxicities, respectively, Kambhampati details. No grade 5 CRS or neurologic events occurred. The agent was also associated with immune effector cell-associated neurotoxicity syndrome (ICANS) events and certain infections, Kambhampati notes. However, the overall data appeared promising and substantiated the product's approval, she states.

Taking these findings into account, and acknowledging the selective eligibility criteria often present in clinical trials like ZUMA-2, Kambhampati says that the assessment of real-world safety and efficacy outcomes for brexu-cel was deemed necessary. Accordingly, a subgroup analysis was designed to ascertain how these clinical trial findings manifest within a real-world population of patients with relapsed/refractory MCL, Kambhampati says. These patients had progressed on up tp 3 or more prior lines of therapy.

In addition to identifying potential disparities in real-world clinical practice, the study sought to examine the influence of prior treatments, such as bendamustine, BTK inhibitors, autologous stem cell transplant, and the number of prior lines of therapy, on these outcomes, Kambhampati concludes.

Dr Kambhampati had no relationships to disclosure

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Swetha Kambhampati, MD, discusses the rationale for evaluating outcomes with in a subgroup anlaysis of patients with relapsed/refractory mantle cell lymphoma, and how prior data from the phase 3 ZUMA-2 study supported the inception of this trial.
 

Dr Kambhampati on the Rationale For Evaluating Real-World Outcomes With Brexu-Cel in MCL

Swetha Kambhampati, MD, hematologist/oncologist, assistant professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses how findings from a subgroup analysis of investigating the use of brexucabtagene autoleucel (Tecartus; brexu-cel) in relapsed/refractory mantle cell lymphoma (MCL) may support the continued exploration of this agent in earlier lines of therapy.

This real-world study identified patients in the CIBMTR observation database whose disease had previously progressed on the BTK inhibitor, bendamustine (Avastin), or autologous stem cell transplantation (ASCT). Patients were also required to have received either up to 2 prior lines of therapy, or 3 or more prior lines.

Results showed that patients who received 1 or 2 prior lines of treatment had higher responses and were more likely to achieve a complete response with brexu-cel vs those who had received 3 or more lines of treatment, Kambhampati reports. Moreover, a multivariate analysis revealed that exposure to prior BTK inhibitors or bendamustine did not affect the efficacy or safety of brexu-cel treatment. This was observed even after accounting for other baseline characteristics, she adds. Notably, these real-world safety and efficacy outcomes reflected those observed in clinical trials, such as the phase 3 ZUMA-2 study (NCT02601313), Kambhampati says.

Overall, the findings from this extensive real-world study provide compelling evidence to consider treatment with brexu-cel in earlier treatment lines, Kambhampati continues. The association between elevated response rates and lower levels of prior treatment in this population indicates that early administration of brexu-cel could potentially enhance treatment outcomes, she says. This strategy is also mechanistically supported in patients who have undergone fewer prior treatments have enhanced T-cell quality. Consequently, this could improve patient responses to brexu-cel, Kambhampati explains.

Further evaluation is necessary to validate the benefits of using brexu-cel in the upfront setting, and to refine treatment strategies in this space, Kambhampati concludes.

Swetha Kambhampati, MD, discusses how findings from a subgroup analysis of investigating the use of brexucabtagene autoleucel in relapsed/refractory mantle cell lymphoma may support the continued exploration of this agent in earlier lines of therapy.

Dr Kambhampati on the Potential Use of Brexu-Cel in Earlier Treatment Lines in MCL

Swetha Kambhampati, MD, hematologist/oncologist, assistant professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses key findings from an analysis of real-world efficacy outcomes with brexucabtagene autoleucel (Tecartus; brexu-cel) in heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).

Using the CIBMTR observation database, a subgroup analysis was conducted to assess outcomes with brexu-cel in clinical practice for patients with MCL. Patients included the analysis had previously been treated with a BTK inhibitor, bendamustine, or autologous stem cell transplantation (ASCT), and had received either 1 to 2 or 3 or more prior lines of therapy. The median number of prior lines was 4 (range 1-12).

At total of 380 patients were included in the study from 84 centers across America. The overall response rate (ORR) in the overall population was 90%, including a complete response (CR) rate of 78%, Kambhampati reports. Notably, these response rates are similar to those from the phase 3 ZUMA-2 study (NCT02601313), in which brexu-cel had an ORR of 91% and a CR rate of 68%, Kambhampati adds. The median duration of response (DOR) in this cohort was 21.7 months.

Assessment of patient responses according to previous lines of therapy showed that patients who had received 1 or 2 prior lines had higher response rates and an increased likelihood of achieving a CR vs those who had received 3 or more lines, Kambhampati continues. Additionally, a multivariate analysis was onducted to analyze the effect of treatment types on efficacy outcomes. After adjusting for baseline characteristics like age, sex, and other disease characteristics, the analysis showed that exposure to prior BTK inhibitors or bendamustine did not affect efficacy and safety outcomes, Kambhampati expands. However, patients who previously underwent ASCT had improved progression-free survival, she notes.

Regarding safety, 88% of patients experienced any-grade cytokine release syndrome (CRS) and 60% experienced any-grade immune effector cell-associated neurotoxicity syndrome (ICANS), Kambhampati says. Grade 3 or higher CRS and ICANS events occurred in 10% and 28% of patients, respectively. Prior exposure to bendamustine was also associated with a decreased risk of exhibiting high-grade ICANS and prolonged thrombocytopenia, Kambhampati states. Patients who received 1 or 2 prior lines of therapy had higher rates of severe CRS compared with those who received 3 or more lines, Kambhampati details. 

Ultimately, previous exposure to a given therapy did not greatly affect safety and efficacy with brexu-cel, Kambhampati says. Moreover, these safety and efficacy outcomes in clinical practice reflected those in clinical trials, she emphasizes. Further evaluation is needed to explore efficacy signals with the agent in patients who received it in earlier lines of therapy, Kambhampati concludes.

Swetha Kambhampati, MD, discusses key findings from an analysis of real-world efficacy outcomes with brexucabtagene autoleucel in heavily pretreated patients with relapsed/refractory mantle cell lymphoma.

Swetha Kambhampati, MD

Articles

Dr Kambhampati on the Rationale For Evaluating Real-World Outcomes With Brexu-Cel in MCL

Dr Kambhampati on the Potential Use of Brexu-Cel in Earlier Treatment Lines in MCL

Dr Kambhampati on the Real-world Efficacy of Brexu-Cel in Heavily Pretreated Patients With MCL