An Introduction to Mantle Cell Lymphoma & KTE-X19

Bijal Shah, MD: Hi, I’m Dr Bijal Shah from the Moffitt Cancer Center in Tampa, Florida. I’m an associate professor in the Department of Malignant Hematology, where I focus on the treatment of mantle cell lymphoma.

The prognosis for patients with relapsed/refractory mantle cell lymphoma is still somewhat of a challenge, especially when we talk about advanced relapses, where we’re saying that they’ve relapsed after 2, 3, 4, 5 lines of therapy. A nice review by Anita Kumar and her colleagues at Memorial Sloan Kettering [Cancer Center] was performed, and they show what we’ve all experienced in practice, which is this notion of diminishing returns with each subsequent line of therapy. If we get about 5 years from the first line, we’re going to get 2½ years from the next line, 1 year from the next line, 6 months, and so on. Essentially, when we say specifically, “Let’s fast-forward to the third-line-and-beyond setting,” we’re talking about a median PFS [progression-free survival] of somewhere around 3 to 6 months, again diminishing with each line. When we talk about survival, it’s also dropping off dramatically. We’re talking about a median overall survival once we get into that third-line setting of around 2 years. When we talk about fourth line, it’s more along the lines of about a year and so on. We really are running into considerable difficulties when we talk about the treatment of multiple relapsed and refractory mantle cell [lymphoma].

Kite Pharma–Gilead Sciences submitted to the FDA a request for CAR [chimeric antigen receptor] T-cell therapy approval in mantle cell lymphoma. There are a couple of things to know about this particular CAR T. It’s made a little differently. It’s not called Yescarta, the product that’s currently approved for diffuse large B-cell [lymphoma]. This 1 is currently going by the name KTE-X19. I’m not sure what the official brand name will be. KTE-X19 is unique in that there’s a separation step involved before the CAR T cells are manufactured. Normally, when we talk about treating a patient with diffuse large B-cell lymphoma, we just collect the T cells, and if there are other cells in the product, they can go into the manufacturing. When we talk about KTE-X19, we’re actually very purposefully separating out the T cells from the rest of the product before manufacturing. That process of isolating the CD4 and CD8 T cells does make the product unique, and that change in manufacturing does require a different moniker for the product.

In terms of the priority review, when Kite-Gilead launched the trial, they had already been working with the FDA. This is something where the process is dating back to around 2016, when the trial was getting off the ground and they began having conversations with the FDA to ask what it would take to commercialize this product. What we’re seeing in terms of the BLA [biologics license application] and the rapid turnaround for that BLA is a reflection of all the things that happened beforehand. Certainly, the data we’ve seen are very encouraging and all support that priority review. We’re expecting an answer in August. I’m keeping my fingers crossed. We certainly, as I alluded to earlier, need new therapies for higher-risk variants of mantle cell lymphoma, and the data that we’re seeing coming out of this particular trial suggest this could be a very powerful adjunct.

Transcript Edited for Clarity