Later-Line CD19 and Bispecific Therapies Considered After CAR T

Christopher Maisel, MD (Moderator)

Hematologist/Oncologist

Texas Oncology

P.A. Baylor Sammons Cancer Center

Dallas, TX

DISCUSSION QUESTIONS

• What treatment options could be considered in the third-line setting for relapsed/refractory diffuse large B-cell lymphoma (DLBCL)?
• With the real-world data for third-line therapies, how have treatment algorithms changed in later-line DLBCL?

Christopher Maisel, MD: Real-world effectiveness of loncastuximab after chimeric antigen receptor (CAR) T-cell therapy was presented in February 2024 at the Tandem [Transplantation & Cellular Therapy] Meetings.¹ This was looking at a number of patients who had CD19-expressing CAR T-cell therapy in the second- or third-line setting, and subsequently had disease progression before getting loncastuximab [Zynlonta] monotherapy as third- or fourth-line therapy.

It was a small number of patients, but the overall response rate [ORR] in patients getting loncastuximab in third- and fourth-line post CAR T-cell therapy failure was 73% with a complete response [CR] rate of 34%. For those who got CAR T-cell therapy in the second-line setting and loncastuximab in the third-line setting, [the ORR was 82% and the CR rate was 43%]. Those numbers go down [for CR] if they got third-line CAR T-cell therapy and fourth-line loncastuximab, as we would expect.

These are reasonably good data all in all. They broke it down by responding to CAR T cells and refractory to CAR T cells. There were some responses to loncastuximab even in patients who were refractory to CAR T in the second- or the third-line setting—not as good as those that responded to CAR T cells but there is clearly still some benefit to this drug, albeit in a small cohort, when given in the third and fourth line after CAR T-cell therapy.

We currently have 2 FDA-approved bispecific antibodies in the third-line setting for relapsed/refractory DLBCL [with epcoritamab (Epkinly) and glofitamab (Columvi), along with loncastuximab in the third line]. Considering the real-world evidence from the [Tandem Meetings and] American Society of Hematology Annual Meeting, how have treatment algorithms changed in the third line and beyond for DLBCL and how would you treat these patients?

Khoan T. Vu, MD: I think the data for bispecifics are very encouraging, so I would definitely use bispecifics in this setting.

Maisel: There is no right or wrong answer here. Both loncastuximab and 2 bispecific antibodies are FDA approved and listed by the National Comprehensive Cancer Network in the third-line and beyond setting in DLBCL.

Camille Johnson, MD: I would favor [bispecifics]. The CRs were pretty impressive.

Maisel: So you like the CR rate being higher.

Nithya Palanisamy, MD: The only issue with the bispecifics is the initial hospitalization.

Maisel: Is that a barrier to you giving bispecific antibodies in your practice?

Palanisamy: Yes.

Maisel: Is it due to simply having to put the patient in the hospital or the hospital systems not having the medication on their formulary, or a combination?

Palanisamy: It's a combination.

Fariborz Gorouhi, MD: In small hospitals, in addition to not being on formulary, even if the oncologist is comfortable, usually the rest of the team is not comfortable for the first cycle or so. That's another issue.

Deepa Sashital, MD, PhD: As of yet, all the Texas Oncology sites are not qualified to give it.

DISCUSSION QUESTIONS

• With new agents approved in the relapsed/refractory setting for DLBCL, what is the optimal treatment selection and sequencing strategy for patients in the third-line setting?
• Does your sequencing strategy change if you need to bridge to CAR T-cell therapy?

Maisel: It sounds like the group [leans toward] the third-line regimen with a bispecific antibody first, and then loncastuximab. But what if you need to bridge to CAR T-cell therapy? Would you use a bispecific antibody to bridge to CAR T? Or would you prefer loncastuximab or a different therapy in that space? Or would you use neither of them? Would you use chemotherapy, steroids, etc?

Sashital: Generally, so far, the CAR T centers have been recommending chemotherapy as a bridging therapy.

Gorouhi: I'm worried if we use CD19 [therapies], then it's difficult to use CAR T-cell therapies.

Maisel: I would tend to agree with you. I try to avoid any CD19-targeting therapies prior to CAR T-cell therapy myself.

We talked about bispecifics, and how you treat patients with bispecifics. Are there more comments about treatment in the community setting? We talked about access and barriers being formulary, comfort in the community hospital, and comfort of the primary team taking care of the patient. Are there any other thoughts about giving bispecific antibodies in the community setting?

Vu: I've given bispecific antibodies at our hospital, and the experiences have been positive. Our staff is trained to monitor and manage cytokine release syndrome. It's been positive.

Johnson: I gave my first [bispecific antibody] today for a solid tumor, not for lymphoid malignancy. We had the teaching ahead of time, so I think people felt relatively comfortable. [It was for a patient with]...small cell lung cancer in the second line.

Henry Q. Xiong, MD, PhD: I practice in Fort Worth. We have a few hospitals, and we started using bispecific antibodies in some of the hospitals. It takes a lot of time to educate the staff nurses and other hospitalists on how to watch for the complications and adverse events. We have protocol written for the patients who receive bispecific antibodies so it's durable in the community setting, and we started doing that.

_References:

_{1. Epperla N, Lucero M, Bailey T, et al. Real-world clinical effectiveness of loncastuximab tesirine monotherapy for the treatment of relapsed/refractory diffuse large B-cell lymphoma following chimeric antigen T cell therapy in the US. Presented at: 2024 Tandem Meetings, Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, February 21-24, 2024. Poster 482.}