What is the Role of CAR T-Cell Therapies for R/R DLBCL Patients Following Two Prior Lines of Therapy?

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Dr. Riedell:
Hello, my name is Peter Riedell and I'm from the University of Chicago. This presentation is on the role of CAR T-cell therapies for relapse refractory diffuse large B-cell lymphoma patients following two prior lines of therapy.

So in diffuse large B cell lymphoma, there are several approved agents in the third-line setting. Today we'll specifically focus on CAR T-cell therapy, including Axicabtagene ciloleucel or Axi-Cel, Lisocabtagene maraleucel or Liso-cel, And Tisagenlecleucel or Tisacel.

This slide reviews the three pivotal CD 19 directed CAR T-cell clinical trials including the ZUMA-1 study evaluating Axi-Cel the Juliet trial evaluating Tisacel and the transcend study evaluating Liso-cel. And we can see here that these three trials did differ slightly including the population of patients enrolled along with the application of things like bridging therapy and the median turnaround time.

In the Phase 2 ZUMA-1 trial evaluating Axi-Cel this therapy was found to be highly active in patients with relapse refractory diffuse large B-cell lymphoma including best objective response rate of 83% and best CR rate of 58%. And with a median follow-up of 27.1 months, we can see that median progression-free survival was not reached for patients achieving a complete or partial response.

Now, thankfully we have updated follow-up, which continues to show encouraging overall survival benefits for patients with relapse refractory large cell lymphoma. We see here a median overall survival of 25.8 months in patients and five-year overall survival of 43% among infused patients.

Additionally, the Juliet trial evaluated Tisagenlecleucel in patients with relapse refractory large cell lymphoma. This study demonstrated encouraging best overall response rate at 53% including complete responses in 39% of patients. Additionally, we see really encouragingly high rates of progression-free survival in patients infused with this product, including 31% PFS at 36 months. Additionally, as we can see from the Kaplan Meyer figure here that responses did appear to be durable in patients.

The Transcend trial evaluated Lisocabtagene maraleucel in a similar patient population with relapse refractory diffuse large B-cell lymphoma. In this study, we also see high overall response rates of 73%, including complete responses in 53% of patients. This slide evaluates the progression-free and overall survival. On the left, we have the progression-free survival curves, and we can see here medium progression-free survival of 6.8 months for all infused patients. Although not reached for patients achieving a CR as their best response. On the right-hand side of the slide, we have the overall survival curves which show a median overall survival of 21.1 months. Again, we see encouraging durable responses in patients with an estimated two-year duration of response of 49.5% in progression-free survival. Two years of 40.6% in patients infused with Liso-cel.

We now have an increasing amount of data in the use of CAR T-cell therapy in the real world or commercial setting for multiple centers. This study looks at the utilization of Axicabtagene Ciloleucel and Tisagenlecleucel among centers that had access to both therapies. And we can see here that we see encouraging rates of progression-free survival and overall survival in patients who received Axicel and Tiso-cel with really no significant difference in progression free and overall survival rates among recipients of these different products.

This also looks at the real-world experience utilizing CD19-directed CAR T-cell therapy with Axicaptogene Cleulucel. And we can see here that there is now an emerging story where patients' disease phenotype and disease burden may have an implication on the success of CAR T-cell therapy. And specifically, if we look at outcomes based on ECOC performance status, that we can see that patients that have an impaired ECOG performance status of two to four have worse progression-free survival. And additionally, those patients with an elevated LDH at the time of initiation of lympho depleting chemotherapy have worse progression-free survival compared to their counterparts.

And so, in summary CAR T-cell therapy produces impressive overall response rates and complete response rates in heavily pretreated patients with relapse refractory aggressive large B-cell lymphoma. Specifically, we note that among these varying studies that responses do appear durable for approximately 35 to 45% of patients. Now there are multiple CAR constructs with relatively similar efficacy, although there are certainly differences in the patient populations and trial designs. Reassuringly, we are seeing comparable results in the real-world population which would certainly drive the expansion of this therapy to now a larger population of patients who would potentially benefit. And in summary, we encourage early referral for discussion of CAR T-cell therapy. Thank you for your attention.

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