The CAR-T Versus Bispecific Antibody Debate in Third Line LBCL

Emilie Aschenbrenner, PharmD, BCOP

For the past 5 to 6 years, chimeric antigen receptor T-cell (CAR-T) therapy has been a mainstay of third line treatment for large B-cell lymphoma (LBCL), and has began its move into the second line setting, as well. Despite this, bispecific antibody treatments are a new up and coming FDA-approved alternative to CAR-T in these settings, leading to questions about the advantages and disadvantages of each modality.

Emilie Aschenbrenner, PharmD, BCOP, a hematology coordinator for pharmacy at Froedtert and the Medical College of Wisconsin, and Katie Gatwood, PharmD, BCOP, a stem cell transplant and cellular therapy clinical pharmacist specialist at Vanderbilt University, held a light-hearted debate about CAR-T and bispecific antibodies in this setting at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024. After the debate, CGTLive® sat down with Aschenbrenner to get her views on the main takeaways from the discussion.

CGTLive: Can you give some background context about your session at Tandem 2024?

Emilie Aschenbrenner, PharmD, BCOP: My partner and I presented at the pharmacy conference a bit about CART-cell therapy and now the new bispecific antibodies for LBCL. Essentially, CAR-T has really had a role and established its presence in the last 5 to 6 years in the third line setting, and now in the second line setting, for LBCL. We did kind of a comedic debate about where the bispecifics are now going to fit in—so taking a bite out of that CAR-T space race, essentially.

What were the key points discussed during this debate?

My partner, Katie Gatwood, reviewed the CAR T-cell data in the third line setting for LBCL. Really, what we have in that space is some unprecedented overall survival data now, especially 5 years out. But then I was the counterpart to that debate, [arguing] for bispecific antibodies. These are a great option now for patients in the third line setting and beyond that are maybe not candidates for CAR T-cell therapy or have relapsed after CAR T-cell therapy. What's nice and notable about these therapies is there's less incidence of and duration of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome—those unique toxicities of cellular therapy—and less prolonged cytopenia. As such, they are really a great additional option for patients with LBCL.

What would you say are the big picture ideas that you would want doctors and the broader healthcare community to take away from this discussion?

CAR-T is still a great option for patients that are fit enough to receive CAR T-cell therapy, are near an authorized treatment center, and have a caregiver. But now with these bispecific antibodies we now have consensus recommendations to give them in the community setting, so it's a great option for patients. They don't necessarily need a dedicated caregiver for that full month, like a CAR T-cell therapy patient would. Really, I think we'll become more comfortable with these types of therapies. Even if community settings don't want to do the step up dosing it’s still a great option for them in cycle 2 and beyond.

Can you speak about challenges and areas of interest for further exploration in regard to this debate?

I think there's a couple different responses to that question. We know that in patients that have failed prior CAR-T, the response rates are a little bit lower with the bispecifics. Understanding how patients can still benefit from these type of therapies after CAR-T and what subsets of patients are most likely to benefit [is of interest]. Then we're also really looking to use these earlier in lines of therapy, either as single agents or more likely in combination with chemoimmunotherapy in the first and second line, so there's evolving and ongoing research in that setting as well.

Is there anything else you would like to share?

I think the bispecific antibodies in LBCL are a great option because we have options for formulations of subcutaneous injection versus intravenous infusion. Right now, there’s different labeling for the FDA approved products (epcoritamab versus glofitamab); one is “treat to progression” and one is for a fixed duration. As such, there's options for patients based on their disease state and provider preference there. I also think we'll see more approved in the coming months to years, so there'll be more options for physicians to choose from.

This transcript has been edited for clarity.

Click here for more coverage of Tandem 2024.

REFERENCES
1. Aschenbrenner E. Taking a bite out of CAR-T: Debating use of CAR T-cell therapy vs bispecific antibodies in lymphoma. Presented at: 2024 Tandem Meetings, February 21-24, San Antonio, Texas.