EP. 1: Exploring CAR T-Cell Therapy in Patients with Mantle Cell Lymphoma

In an interview with Targeted OncologyTM, Leslie, assistant professor, Hackensack Meridian School of Medicine, director, Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs, John Theurer Cancer Center, discussed the CAR T-cell product, brexucabtagene autoleucel, and its influence on both MCL and indolent lymphomas.

What do you hope to see from the ongoing ZUMA-2 analysis?

There are a few different cohorts ongoing in ZUMA-2 looking at brexucabtagene. We've got a cohort looking at BTK-naive patients, we have a cohort that's expanded access that allows bridging therapies and more of our real-world population, and then there's a cohort where you can get access to cells if they're out of specification.

I think these data along with data that's emerging from real world experience with brexucabtagene in mantle cell lymphoma, show us that what we see in clinical trials is translating to our real-world population. I'm hoping these data will help convert the accelerated approval into a full, long term FDA approval for this CAR T-cell product in patients with relapsed mantle cells. I think moving forward too, it will be investigated in earlier lines of therapy as we're doing with other CD19 CAR T-cell products across B-cell lymphomas.

Are there any studies or novel CAR T cells that you have your eye on right now?

There's a lot of other studies looking at CD19 CAR T cells across different B-cell malignancies. We've got ZUMA-2 which looked at indolent lymphomas and led to an approval in follicular lymphoma based on overall response rate of 94% and a complete response rate close to 80% in patients with relapsed/refractory disease. I think further follow up from ZUMA-5 [NCT03105336] will let us know if this is a potentially curative option for our patients with the more indolent lymphomas, they can have relapses 10, 20, even 30 years down the line.

We have CD19 CAR T approved in DLBCL and that is being investigated in earlier lines of therapy. Recently published in a New England Journal of Medicine is the ZUMA-7 [NCT03391466] study that looked at CD19 CAR T-cell therapy axicabtagene ciloleucel

[axi-cel; Yescarta] as second line therapy compared to standard of care, high dose therapy and autologous stem cell transplantation. This was the first initiated and first to meet its primary efficacy analysis among many different studies in this space trying to transform second line DLBCL therapy, away from high dose chemo and consideration of autologous stem cell transplant, particularly for patients with chemo-sensitive disease and instead sparing patients the toxicity of high dose chemo and transplant and allowing them to go straight to CD19 CAR T-cell therapy in the second line setting.

We are taking the CD19 CAR T cells and adjusting the types of lymphoma where we can use them and the lines of therapy where we can use them. Moving forward, what's probably transforming this space the most are potentially CAR T-cell products that target different antigens on the tumor cell, but also dual targeting CAR T, so these targets CD19 and there are other CAR T products that target more than 1 tumor antigen. Instead of autologous products, there are allogeneic off the shelf or their cell therapy products that may be T cells, they may be NK cells. There are some other ways of conjugating an antibody to an effector T-cell to have a CAR T-like effect with a more simple and potentially less expensive manufacturing process. There are a lot of ways that this space is moving forward quite rapidly in a way that's incredibly hopeful and promising for our patients.

What are your thoughts on the current landscape for mantle cell lymphoma and how the future looks?

I would say it is a exciting time in cancer in general and lymphoma therapies are advancing at the most rapid rate we've seen since I've been in medicine. It's really a very promising time for our patients. Even as a lymphoma specialist, it's hard to stay up to date sometimes because things are changing so rapidly. I feel very hopeful, our patients have all the reasons to feel very hopeful, and as we harness the power of the immune system, I think things are only going to continue to get better.

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