Peter Riedell, MD, is an associate professor of medicine in the Section of Hematology/Oncology at the University of Chicago.

Peter Riedell, MD, highlights the rationale for investigating CAR T-cell therapy rapcabtagene autoleucel in relapsed/refractory DLBCL.

Dr Riedell on the Rationale for Evaluating Rapcabtagene Autoleucel in R/R DLBCL 

“In diffuse large B-cell lymphoma, CAR T-cell therapy has been heavily utilized and now adopted in the treatment paradigm. However, there are some challenges that exist in operationalizing this therapy, and one of them is we’ve seen patients have relapsed or refractory disease to CAR T-cell therapy based on components of the composition of the CAR T-cell product.”

Peter Riedell, MD, associate professor of medicine, Section of Hematology/Oncology, the University of Chicago, highlights the rationale for evaluating the CAR T-cell therapy rapcabtagene autoleucel (YTB323) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a phase 2 study (NCT03960840).

In the DLBCL treatment paradigm, the utility of CAR T-cell therapy has been established and commonly utilized, Riedell begins. However, patients can still experience relapse and become refractory to CAR T-cell therapy, which could potentially be based on the components and composition of the CAR T-cell product, he explains. Better persistence and proliferation were associated with products enriched in stem-like T-cells, he adds.

 showed that at a median follow-up of 16.4 months, data from an interim analysis in the phase 2 study demonstrated an overall response rate of 88.3% (95% CI, 77.4%-95.2%) and a complete response (CR) rate of 65.0% (95% CI, 51.6%-76.9%). Of note, CR rates at 3, 6, and 12 months were 54.6%, 56.8%, and 47.4%, respectively.

Another challenge that contributed to the rationale of the study included disease progression during the manufacturing process of the CAR T-cell product, Riedell emphasizes. He notes that the utilization of the T-charge platform helps by harvesting T-cells within 48 hours of culture and can lead to improvements in turnaround time regarding the vein-to-door time. Based on the interim analysis from the study, the median vein-to-door time was 13 days globally and 9 days in the United States, which compares favorably to other available commercial products, Riedell concludes.

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“There are a lot of attractive features in the context that [rapcabtagene autoleucel is] associated with high efficacy and also seems like a safe product. Therefore, it might certainly have further utilization, should we see some more mature data and further follow-up of these patients. [Rapcabtagene autoleucel] may be an attractive agent to consider in this space.”

Peter Riedell, MD, associate professor of medicine, Section of Hematology/Oncology, David and Etta Jonas Center for Cellular Therapy, the University of Chicago, provides an update on the efficacy and safety outcomes of rapcabtagene autoleucel (YTB323) in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a phase 2 trial (NCT03960840).

 demonstrated that patients (n = 63) treated with rapcabtagene autoleucel—a next-generation CD19-directed CAR T-cell therapy—produced an overall response rate (ORR) of 88.3% (95% CI, 77.4%-95.2%), which included a complete response rate of 65.0% (95% CI, 51.6%-76.9%). The primary end point of best overall response of CR was met.

Additionally, the 12-month progression-free survival (PFS) rate was 48.2% in the overall population, and the median PFS was 11.9 months (95% CI, 5.6-not evaluable [NE]). In patients who achieved a CR (n = 30), the median PFS was NE (95% CI, 14.5-NE), and the 12-month PFS rate was 79.3%.

Safety data demonstrated that any-grade cytokine release syndrome (CRS) was reported in 44.4% of patients; however, most instances were low-grade, Riedell explains. Grade 3 and grade 4 CRS each occurred in 3.2% of patients, and no grade 5 events were reported. Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed at grade 1 in 3.2% of patients, grade 3 in 3.2% of patients, and grade 4 in 1.6% of patients.

Riedell explains that these findings suggest that rapcabtagene autoleucel may offer a manageable safety profile compared with other CAR T-cell therapies, which have traditionally been associated with higher rates of severe CRS and ICANS. Ongoing follow-up analyses to assess the durability of these responses will be key to further elucidate what role rapcabtagene autoleucel could play in the relapsed/refractory DLBCL treatment paradigm, he concludes.

Peter Riedell, MD, discusses efficacy and safety of rapcabtagene autoleucel in patients with relapsed/refractory diffuse large B-cell lymphoma. 

Dr Riedell on Efficacy and Safety of Rapcabtagene Autoleucel in R/R DLBCL

Peter Riedell, MD, assistant professor of Medicine, Section of Hematology and Oncology, The University of Chicago Department of medicine, discusses the clinical utility of 

 mutation testing when navigating treatment options for patients with relapsed/refractory follicular lymphoma (FL).

tazemetostat (Tazverik) was approved by the FDA in 2020 for patients with relapsed/refractory EZH2-positive FL

 who have received at least 2 prior systemic therapies or who have relapsed/refractory disease with no other available satisfactory treatment options. Additionally, an associated EZH2 Mutation Test was concurrently approved by the FDA as a companion diagnostic for this population.

 mutation testing can help guide treatment decisions and optimize the selection of appropriate therapeutic interventions, Riedell begins. During treatment selection, this diagnostic tool’s predictive value may provide valuable insights into patient responses to tazemetostat in clinical practice, he expands.

Next-generation sequencing (NGS) is typically employed to identify 

mutations, Riedell continues. However, it is crucial to note that 

mutations are relatively rare, he states. Ridell explains that approximately 20% of patients harbor these mutations, though the percentage may be lower outside of a clinical trial setting. Additionally, current research indicates that tazemetostat demonstrates efficacy in patients with both 

-mutant disease, Riedell notes, although tazemetostat may provide more benefit to those expressing 

mutations. Consequently, the decision to initiate tazemetostat treatment is not solely determined by the presence or absence of this mutation, Riedell emphasizes.

Ultimately, this personalized approach can ensure that patients receive the most suitable treatment options, thereby improving their chances of a favorable response to therapy, Riedell concludes.

Peter Riedell, MD, discusses the clinical utility of EZH2 mutation testing when navigating treatment options for patients with relapsed/refractory follicular lymphoma.
 

Dr. Riedell on the Clinical Utility of EZH2 Mutation Testing in Relapsed/Refractory FL

Peter Riedell, MD, assistant professor of Medicine, Section of Hematology and Oncology, The University of Chicago Department of medicine, discusses the use of axicabtagene ciloleucel (axi-cel; Yescarta) in high-risk large B-cell lymphoma (LBCL), as evaluated on the phase 2 ZUMA-12 trial (NCT03761056).

The ZUMA-12 trial evaluated the efficacy and safety of axi-cel as a first-line treatment in patients with high-risk LBCL.

The trial examined a high-risk patient population and utilized a dynamic risk assessment with a PET/CT scan after 2 complete cycles of therapy, Riedell says. Patients that did not achieve a complete response, determined by a Deauville score of 3 or lower, were then eligible to participate on the trial, Riedell explains. T cells were extracted from enrolled patients, and they were moved to treatment with lymphodepleting chemotherapy, followed by the CAR T-cell infusion, Riedell says.

Although the ZUMA-12 trial provided encouraging results with progression-free survival and complete response rates, additional follow-up of the study is required to understand the implications of axi-cel in these patients, Riedell continues. A randomized trial will be necessary to potentially bring axi-cel to the first-line setting, Riedell concludes.

Peter Riedell, MD, discusses the use of axicabtagene ciloleucel in high-risk large B-cell lymphoma, as evaluated on the phase 2 ZUMA-12 trial.


Dr. Riedell on the Examination of Axi-Cel Therapy in High-Risk LBCL

Peter Riedell, MD, assistant professor of medicine, University of Chicago Medicine, discusses unique data points of a landmark analysis conducted in mantle cell lymphoma (MCL).

Several unique data points were noted from the analysis, Riedell explains. For example, the data showed that when employing a multivariate analysis, the effect of relapse on overall survival (OS) varied with time, Riedell says. Additionally, the effect of relapse was the greatest at early time points after patients had undergone an autologous hematopoietic cell transplant (AHCT), Riedell explains. Moreover, patients who relapsed by the 6-, 12-, or 18-month landmark time points following AHCT had the worst outcomes overall, Riedell says.

Moreover, patients aged 60 years or older had worse OS at the various landmark time points compared with younger patients, which is consistent with other previously published data, Riedell concludes.

Peter Riedell, MD, discusses unique data points of a landmark analysis conducted in mantle cell lymphoma. 

Dr. Riedell on Unique Data Points from an Analysis in MCL 

Peter Riedell, MD, assistant professor of medicine, University of Chicago Medicine, discusses the patient population and design of a dynamic landmark analysis conducted in patients with mantle cell lymphoma (MCL). 

The analysis focused on evaluating the effect of time to relapse on OS in adult patients with MCL who were treated with up to 2 lines of rituximab (Rituxan)-based induction therapy, followed by frontline autologous stem cell transplantation (ASCT), according to Riedell. In an effort to include a homogenous population, the analysis only included patients who underwent ASCT within 1 year of their diagnosis, Riedell explains. Patients who were transplanted between 2000 and 2018 were evaluated, Riedell adds.

Primary end points included overall survival (OS) and post-relapse OS, Riedell adds. The dynamic landmark analysis was employed at 6-month intervals to evaluate the effects of relapse on OS while adjusting for pertinent patient- and disease-related variables, Riedell concludes.

Peter Riedell, MD, discusses the patient population and design of a dynamic landmark analysis conducted in patients with mantle cell lymphoma.

Dr. Riedell on an Analysis Evaluating the Effect of Time to Relapse on OS in MCL

Peter Riedell, MD, assistant professor of medicine, University of Chicago Medicine, discusses the effects of time to relapse on outcomes in mantle cell lymphoma (MCL).

Findings from an analysis examining the effect of time to relapse on overall survival (OS) in patients with MCL following frontline treatment with high-dose therapy and autologous hematopoietic cell transplantation (AHCT) demonstrated that relapse in MCL following AHCT defines a high-risk group with inferior post-relapse OS.

Other data in other non-Hodgkin lymphoma subtypes like follicular lymphoma have also shed light on how the timing of relapse affects long-term outcomes, Riedell explains.

Ultimately, these data suggest that treatment strategies should be adapted based on timing of relapse following AHCT and that these higher-risk patients should be considered for clinical trials or novel approaches, such as CAR T-cell therapy, Riedell concludes. 

Peter Riedell, MD, discusses the effects of time to relapse on outcomes in mantle cell lymphoma. 



Dr. Riedell on the Effects of Time to Relapse on Outcomes in MCL 

Peter Riedell, MD, assistant professor of medicine, University of Chicago Medicine, discusses the rationale to evaluate survival outcomes after transplant in mantle cell lymphoma (MCL).

MCL is a rare subtype of non-Hodgkin lymphoma in which survival outcomes are heterogenous, Riedell says. For most patients, the standard treatment approach includes intensive induction therapy followed by consolidative autologous stem cell transplant. However, some patients do not derive long-term benefit from this regimen, Riedell explains. 

As such, during the 2021 ASCO Annual Meeting, findings from a study evaluating the effect of time to relapse on overall survival in patients with MCL who underwent this frontline therapeutic approach were presented, Riedell concludes.

Peter Riedell, MD, discusses the rationale to evaluate survival outcomes after transplant in mantle cell lymphoma.



Peter Riedell, MD

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