Real-World Tisagenlecleucel CAR T-Cell Data Mirrors Clinical Trial Data in DLBCL

January 13, 2020
Nichole Tucker

The real-world efficacy and safety demonstrated with tisagenlecleucel, a chimeric antigen receptor T-cell therapy for the treatment of patients with diffuse large B-cell lymphoma, was similar to results from the pivotal JULIET trial, according to Samantha Jaglowski, MD professor at the Ohio State University Comprehensive Cancer Center patients.

Samantha Jaglowski, MD

The real-world efficacy and safety demonstrated with tisagenlecleucel (Kymriah), a chimeric antigen receptor-(CAR) T-cell therapy for the treatment of patients with diffuse large B-cell lymphoma (DLBCL), was similar to results from the pivotal JULIET trial, according to Samantha Jaglowski, MD, professor at the Ohio State University Comprehensive Cancer Center patients.

The real-world data gathered from the Center for International Blood and Marrow Transplant Research (CIBMTR) CT registry showed a median overall response rate (ORR) of 59.6% for 28 out of 47 patients with DLBCL, and of those patients, 38.3% achieved a complete response (CR) (n = 18).

The safety assessment showed grade 3 or higher cytokine release syndrome (CRS) in 4.3% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in another 4.3% of patients. These toxicities were treated with tocilizumab (Actemra) and corticosteroids in 40.9% of the patients who developed CRS and 9.1% of those with ICANS. CRS developed within a median of 4.5 days and lasted for an average of 5 days.

Death occurred in 29.8% of the study participants (n = 14 ), and all were related to disease progression. No patients died as a result of tisagenlecleucel-related toxicities.

In the JULIET trial, treatment with tisagenlecleucel resulted in a 54% ORR, which included CRs in 40% of patients. The safety profile observed in the JULIET trial was also consistent with the real-world study, as 22.6% of patients developed grade 3/4 CRS, and 11.3% had ICANS.

The similarities observed in the real-world study and the clinical trial of tisagenlecleucel in patients with DLBCL confirms the importance of real-world registries, said Jaglowski. If community clinics begin to submit case information to the CIBMTR, the CT registry will have more information on patients across all age groups, including elderly patients who are typically excluded from clinical trials, she added.

In an interview withTargeted Oncologyat the 2019 American Society of Hematology (ASH) Annual Meeting, Jaglowski discussed the real-world data of tisagenlecleucel CAR T-cell therapy in patients with DLBCL and how it relates to the pivotal JULIET study. She also shared recommendations for submitting data to real-world registries to improve the availability of information across different demographics of patients with DLBCL.

TARGETED ONCOLOGY: What was the purpose for this real-world analysis?

Jaglowski: In September of 2019, the CIBMTR and Novartis formed a partnership to track long-term patients who were treated with cellular therapies in the United States, including tisagenlecleucel.

TARGETED ONCOLOGY: What methods were used to complete the analysis?

Jaglowski: The CIBMTR is a large database that collects longitudinal data on patients treated with cellular therapy. In this study, patients were divided into 4 data sets. There's an infusion set, which includes information on patients who have received the cellular therapy product. The safety data set includes patients who have submitted their baseline forms along with 3-month safety forms. The efficacy data set includes participants who submitted baseline and 3-month efficacy forms. There is also a manufacturing data set which is done in conjunction with Novartis. In the manufacturing data set, patients are matched based on having a manufacturing batch number so that information on the product itself can be correlated with information about patient outcomes. About 90% of patients in each of the data sets have manufacturing data.

TARGETED ONCOLOGY: What were the results of the study?

Jaglowski: The results were favorable, although we evaluated patients in a real-world setting who are largely older than those treated in the clinical trial population. The response rates are very similar to what was reported in the pivotal JULIET study, although the follow up was short.

The safety profile appears to be improved. We see much less grade 3 and 4 cytokine release syndrome in the real-world compared to the clinical trial setting. This improvement may be because patients were treated with tocilizumab (Actemra) for CRS at lower grade than what was recommended in the clinical trial setting.

TARGETED ONCOLOGY: What are the implications of these findings?

Jaglowski:The implications of this research are striking. For one, tisagenlecleucel appears to be as safe or safer in the real-world setting as in the clinical trial setting. We're also seeing some interesting signals in terms of efficacy combined with cell dosing. Although this is not statistically significant yet, it could be informative moving forward.

TARGETED ONCOLOGY: What is important for community oncologists to take away from this research?

Jaglowski: For physicians treating patients with these cellular therapies in the community, it's important to consider submitting data to the CIBMTR so that we can continue to study patients in this broader setting to get more information on how these therapies can be used.

TARGETED ONCOLOGY: What are the next steps with this research?

Jaglowski: This is the first report out of the tisagenlecleucel DLBCL data. The next steps are going to be to accrue more patients. The goal is to collect 2,500 patients, and currently, there are just over 100 patients enrolled. The goal is for this to be a large repository of data and we are not there yet.

TARGETED ONCOLOGY: What other promising CAR T-cell therapy research was presented at ASH?

Jaglowski: The study that many people are excited about is the ZUMA-2 trial. This is research on patients with ibrutinib (Imbruvica)-refractory mantle cell lymphoma (MCL). It showed a nearly 67% CR rate in a very challenging patient population. I think this is exciting and potentially game-changing for patients with MCL.


Tisagenlecleucel Chimeric Antigen Receptor (CAR) T-Cell Therapy for Adults with Diffuse Large B-Cell Lymphoma (DLBCL): Real World Experience from the Center for International Blood & Marrow Transplant Research (CIBMTR) Cellular Therapy (CT) Registry. Presented at: 2019 ASH Annual Meeting; December 7-10, 2019; Orlando, FL. Abstract 766.