Michael Wang, MD, Professor, Department of Lymphoma & Myeloma, MD Anderson Cancer Center, Houston, Texas, discusses expanding indications for CAR-T cell therapies, including brexucabtagene autoleucel, for patients with mantle cell lymphoma (MCL). These data were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcript

Hello. My name is Michael Wang. I’m the Puddin Clarke Endowed Professor in the Lymphoma Myeloma Department at MD Anderson Houston, Texas. I'm the overall PI, principal investigator, of the ZUMA-2 clinical trial.

The need for a clinical trial using CAR-T cell therapies such as ZUMA-2 was based on the fact that there was an unmet, urgent clinical need. The unmet clinical need came from the fact that we treat mantle cell lymphoma (MCL) chemotherapy as a targeted therapies, but those therapies are not curative.

After these therapies, the patient with lymphoma gets more aggressive when they relapse and possess a life-threatening disease that's not met by any other currently existing therapies for this challenge. Therefore, we conducted this multicenter international clinical trial evaluating the CD19 CAR-T cell therapy, what is called brexucabtagene autoleucel, in relapsed MCL patients.

Let me explain to you. After the patient has progressed or relapsed after BTK inhibitors after 3 prior lines of therapy, they have only about less than a year to live. Their survival is about 6 to 10 months without effective therapy.

We wanted to conduct this CAR-T cell therapy with the CD19 CAR-T cells to change this fact. That’s why we did this ZUMA-2 clinical trial. Over 100 patients were (enrolled) in this clinical trial, but 60 patients were involved in the primary analysis using brexucabtagene to treat relapse MCL.

Nearly all the lymphoma patients enrolled on this trial were refractory or resistant to prior BTK inhibitors such as ibrutinib, and acalabrutinib, and some of them are intolerant to these drugs.

This patient were treated with brexucabtagene autoleucel in a procedure like follows. First, we do leukapheresis, to collect the T cells, and then we subject that for the cell manufacturer. Then after it's ready, we started the conditional chemotherapy with Cytoxan (cyclophosphamide) and fludarabine (alone) combination. Five days after that we infuse the cells. We include 2 million cells per kilogram on this protocol. Then we admit the patient to the hospital for 1 or 2 weeks and manage the CRS neurotoxicity and the infections, and any other toxicities.

After that at day 30 we will do a PET/CT scan to see the response rate and then at day 90, 3 months after we do scans then we do that periodically after that. Best response are achieved for this trial was 93 overall response rate; 67 percent of them are complete responder's meaning all the lymphomas disappeared before the scans on all the responding patient—the amount of 60 patients.

The efficacy, the response rate, and the CR rate was unprecedented. It totally surprised all the investigators because without a CAR-T cell therapy in the past—if the patient relapsed after 3 prior lines of therapy and were resistant refractory to BTK inhibitors, their response rate to whatever therapy is less than 50 percent, and they only have a very short period of time to live.

The CAR-T cell therapy totally changed that their response rate is 93 percent. CR rate is 67 percent, so this is really a milestone achieved in relapsed MCL for all our patients and their families.

After the FDA approved this product to be used in relapsed MCL based on the data from our ZUMA-2 clinical trial, this product is being used every day to see patients with relapse MCL.

In this coming American Society of Hematology (ASH) Annual Meeting, 2 studies will be presented. One is from Europe using brexucabtagene in the real-world European patient. Another one is a multicenter study, including my center, the real-world practice of brexucabtagene autoleucel and their efficacy.

I can tell you that the efficacy in the real world is not much different from what we achieved in the academic clinical trial. This is really exciting.

First of all, the FDA approved brexucabtagene, not only for the study the indication in BTK resistant or refractory patients, but they also approved this product to use in relapsed MCL even in the patient that did not receive any BTK inhibitors.

This is a expanded indication from the FDA recognizing those patients will need this therapy immediately without further delay. In the academics, and we welcome this very justified, broadened indication.

In order to confirm this, we are running an expanded cohort for those patients who have relapsed mantle cell lymphoma without BTK inhibitors. We would certainly want to use this brexucabtagene autoleucel in the frontline setting.

There is real world data coming up from Europe and the US model center to confirm the findings assuming the ZUMA-2. There'll be a lot of combination studies coming up. Studies based on a MRD combination of CAR-T cells without BTK inhibitors and a lot others to come.

We are in the era of CAR-T cell therapy so not only those CAR-T cells are targeting CD19, other CAR-T cells targeting R1 antibodies, CD70, and many others are coming up. Also, there's a lot of bispecific antibody trials coming up as well.