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ASH 2022 | Latest advances in CAR-T therapy for CLL and Richter’s transformation

Adam Kittai, MD, Ohio State University, Columbus, OH, provides insight into ongoing studies investigating CAR-T therapy for patients with chronic lymphocytic leukemia (CLL) and Richter’s transformation (RT), including lisocabtagene maraleucel (liso-cel) alone or in combination with ibrutinib, axicabtagene ciloleucel (axi-cel), and ROR1-directed CAR-T therapy in CLL, and brexucabtagene autoleucel (brexu-cel), and liso-cel and zanubrutinib in RT. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.

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Transcript (edited for clarity)

Classically, the first cellular therapies that were used were actually used in CLL. We actually saw some nice articles written recently about these three patients who received CAR-T for their CLL back about 10 years ago. Unfortunately, the use of CAR-T for CLL hadn’t really panned out over the last 10 years, where we were seeing some just not great overall response rates for patients with CLL, it’s likely due to CLL induced immune dysfunction...

Classically, the first cellular therapies that were used were actually used in CLL. We actually saw some nice articles written recently about these three patients who received CAR-T for their CLL back about 10 years ago. Unfortunately, the use of CAR-T for CLL hadn’t really panned out over the last 10 years, where we were seeing some just not great overall response rates for patients with CLL, it’s likely due to CLL induced immune dysfunction. Specifically for T-cells, we see a lot of exhaustion markers for T-cells in patients who have CLL.

But there has been some recent breakthroughs. For one, there’s the TRANSCEND study which looked at the CAR-T product liso-cel and it used liso-cel as a monotherapy plus liso-cel plus ibrutinib. In recent studies, there has been shown that patients who are treated with ibrutinib, the BTK inhibitor, there’s some reversal in that T-cell exhaustion leading to improves CAR-T cells, CAR-T expansion, and potentially a decrease in side effects induced by CAR-T. So we’re excited to see how liso-cel does for patients with CLL.

There is a trial that’s currently open with BMS that’s using the anti-ROR1 CAR-T, which we’re looking forward to seeing as well. There’s some various other trials throughout the country. There’s one at OSU that’s combining the anti-CD19, 20, and 22 CAR-T for CLL amongst other lymphomas and B-cell malignancies. So I think that the story around CAR-T for CLL is still to be told, but there is some developments and we’re looking forward to see how liso-cel does moving forward.

In terms of Richter’s transformation, we at OSU published our data of our nine patients who received CAR-T cell therapy for Richter’s transformation. The majority of these patients had received concurrent BTK inhibitor, usually ibrutinib, and there was a couple of acalabrutinibs there as well. We are now looking to publish our long-term findings of 14 patients treated with axi-cel, and we are excited to say that it still looks like it works.

But really that’s retrospective data. This is really selected patients who were able to get CAR-T. There needs to be prospective trials run for patients with Richter’s transformation. There are now two trials that I know that are available for patients. One that’s in the pipeline, one that’s being opened. One is going to be the brexu-cel product through Kite. It’s a basket trial for rare diseases that includes Richter’s transformation, hairy cell leukemia, Burkitt’s lymphoma. Then I have an investigator-initiated trial that’s going to combine zanubrutinib plus liso-cel for Richter’s transformation as well. So I think that the availability of cellular therapies for Richter’s transformation is coming and we are excited to see where this story goes as well.

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Disclosures

Abbvie: Consultancy; Astrazeneca: Consultancy, Research Funding; Beigene: Consultancy; Janssen: Consultancy.