Assessing Available CAR T-Cell Agents for DLBCL

Frederick Locke, MD, a medical oncologist and translational researcher in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, discusses the available chimeric antigen receptor (CAR) T-cell therapies available for patients with diffuse large B-cell lymphoma (DLBCL) and where off the shelf therapies like ALLO-501 and ALLO-501A fit in this treatment paradigm.

As Locke explains, there are 3 FDA approved CAR T cell therapies for this patient population, axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), lisocabtagene maraleucel (Breyanzi). All 3 of these therapies are approved in the third line or later for patients with large B-cell lymphoma, but only axicabtagene ciloleucel and lisocabtagene maraleucel are approved as second line therapies due to results from the phase 3 ZUMA-7 (NCT03391466) and TRANSFORM (NCT03575351) studies, respectively.

However, for patients to obtain these therapies they have to undergo the process of leukapheresis. This process removes blood from the patient’s bloodstream and separates white blood cells from red blood cells and plasma from platelets. This is then manufactured as part of the CAR T-cell therapy and then given to patients, but this process takes time which the patient may not have as their disease progresses. This where off the shelf CAR T-cell therapies ALLO-501 and ALLO-501A could come in and fill the gap caused by waiting for treatment manufacturing. ALLO-501 is being studied in the phase 2 ALPHA2 study (NCT04416984) to assess patients’ objective response rate to this therapy.

Transcript:

0:08 | So, the current landscape of CAR T-cell therapy for DLBCL includes 3 FDA approved treatments; axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. Now, 2 of those are approved as second line therapy based upon recently reported randomized phase 3 trials, that's axicabtagene ciloleucel, or axi-cel, and lisocabtagene, or liso-cel. Those 2 are approved as second line therapy [and] all 3 are approved as third or later line therapy for [patients with] large B-cell lymphoma.

0:41 | These are autologous CAR T cells, meaning we take the patient's own T-cells out of their blood through a procedure called leukapheresis. So, they have to sit on a machine for half a day, the cells get shipped to a manufacturing facility where they're turned into CAR T cells, [and] that process takes at a minimum 3 weeks, and in fact, oftentimes can take 4 to 6 weeks to get those cells back. And so, patients have to wait, and some patients progress while they're waiting. And so, an off the shelf product like ALLO-501 or ALLO-501A would be beneficial, because we could just give it to the patient without having to wait for making these autologous CAR T-cell products.