Kristin M. Zimmerman Savill, PhD, Cardinal Health Specialty Solutions, Dublin, Ohio, discusses real-world characteristics and treatment outcomes of patients with diffuse large B-cell lymphoma (DLBCL) treated with the CAR-T therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel).

This study was presented at the 2021 ASH Annual Meeting.

Transcript 

My name is Kristin Zimmerman Savill. I go by Kristi. I am a principal scientist with Cardinal Health in Cardinal's real-world evidence and insights division.

Today, I just wanted to talk a little bit about work that was presented at ASH 2021 titled “Real-world Treatment of Patients With Large B-cell Lymphoma in the United States With Chimeric Antigen Receptor T-cell Therapy.”

First, I just wanted to talk about what led myself and my co-investigators to conduct the study, so some background. The real-world evidence and insights team at Cardinal Health is dedicated to generating meaningful insights from the analysis of real-world data that comes from sources outside of the clinical trial setting.

So-called real-world evidence can be very powerful as it can demonstrate the effectiveness and safety of therapeutic strategies, as well as treatment patterns, biomarker testing patterns, and finally, prevalence in the broader population. Ultimately, these types of insights may inform drug development, regulatory, as well as clinical decision making.

We can all agree that CAR T-cell therapy represents one of the most innovative recent therapeutic advances in oncology. There have been impressive clinical responses observed in indications including, certain types of lymphomas, ALL, as well as multiple myeloma.

Now that the very first two FDA-approved CAR T-cell therapies approved for the treatment of patients with relapsed or refractory DLBCL after 2 or more lines of systemic therapy have been on the market in the US for somewhere between 3 to 4 years.

Myself and my team, we were interested in conducting a real-world claims-based study in order to gain insights into the treatment journey and the clinical outcomes of patients that have received these CAR T-cell therapies in real-world practice, so outside of clinical trials.

In terms of how we conducted this study, we analyzed patient claims data from the Symphony Integrated Dataverse or IDV. This is a large US claims database, which contains claims for somewhere around 280 million active unique patients representing over 63% of prescriptions with full life cycle data, 62% of medical claims and about a quarter of all hospital-based claims.

Patients included in this study had a diagnosis code of DLBCL. They were treated with the CAR T-cell therapies, axi-cel or tisa-cel anytime from the date of approval of that therapy through March 31, 2021. Patients did not receive CAR-T as part of a clinical trial.

Just to summarize our findings, we identified 88 different study-eligible patients with DLBCL. They were distributed across each of the four US census regions. These patients received CAR T-cell therapy, a median of 14 months after they were initially diagnosed with DLBCL and a median of 3.7 months following discontinuation of the treatment prior to CAR-T.

What we found was interesting was that based on the claims in this database, approximately 43% of patients actually received axi-cel or tisa-cel after just 1 prior line of therapy, not after the failure of 2.

However, we do need to keep in mind that a limitation to this type of claims-based study is the potential for missing data. That might pertain to data related to lines of therapy. We need to incorporate that in our interpretation of the data here.

Among those 88 patients, approximately half received axi-cel, and approximately half received tisa-cel. Claims that were identified for these patients indicated that the CAR T-cell therapy was administered in the inpatient setting for a little over half of patients who received axi-cel, and actually in the outpatient setting for 76% of patients who received tisa-cel.

Though, again, I should note that hospital claims are somewhat underrepresented in the IDV database that we utilized here.

Median follow-up time was less than eight months. It was 7.8 months from axi-cel or tisa-cel therapy. Within that follow-up period, 18% of patients receive systemic therapy following axi-cel or tisa-cel treatment with a median of just under 6 months, so 5.9 months time to next treatment after CAR-T.

In terms of the main takeaways and the significance of these results, I first just want to highlight that point that we saw. Our data was suggesting that just over 40% of patients actually receive axi-cel or tisa-cel prior to the failure of 2 lines of prior therapy. Hence they were receiving CAR-T off label.

Again, we have that caveat of potential missing data related to lines of therapy that may have of impacted the findings. Another key result here was, again, keeping in mind that underrepresentation of hospital claims. It was notable that CAR-T was administered in the outpatient setting for just under half of patients who got axi-cel and about three-fourths of patients who received tisa-cel.

A third main takeaway here was the fact that despite short follow-up times, so less than 8 months from initiation of CAR-T, about 1 in 6 patients appear to have relapse disease based on the need for subsequent systemic therapy. That number might even be higher with longer follow-up times.

That's based on results that were published earlier this year in the New England Journal of Medicine by Chung et al, which demonstrated that 57% of relapsed or refractory DLBCL patients had relapsed within 5 years post CAR T-cell therapy. Mostly within the first year of treatment.

Overall, our claims-based study has provided valuable insights. We can now continue to build on these findings in an effort to understand real-world clinical outcomes among patients treated with CAR-T.

In particular, I think that the use of real-world evidence to help identify particular patient populations in which CAR T-cell therapy is successful will be very important in our overarching mission to help to identify the right treatment for the right patient at the right time.

Zimmerman Savill KM, Klink A, Liassou D, et al. Real-World Treatment of Patients with Large B-Cell Lymphoma in the United States with Chimeric Antigen Receptor T-Cell Therapy. Presented at the ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA and Virtual. Abstract 4096.