Navigating CAR T-Cell Therapy Decisions in Relapsed B-Cell Lymphoma

Priyanka Pophali, MD, MBBS

Use of chimeric antigen receptor (CAR) T-cell therapy still poses questions in relapsed B-cell lymphoma. Participants from Wisconsin and Minnesota debated the optimal timing for CAR T-cell therapy referrals, mentioning considerations such as Deauville scores after frontline therapy and logistical hurdles at a virtual Case-Based Roundtable meeting. The meeting was moderated by Priyanka Pophali, MD, MBBS, an assistant professor and director of the Survivorship Research Program at the University of Wisconsin - Carbone Cancer Center. The discussion covered the value of early consultation and the preference for CAR T-cell therapy over bispecifics due to its "one-and-done" potential despite patient accessibility barriers.

DISCUSSION QUESTIONS

• How comfortable are you referring patients to CAR T-cell therapy in the second line?
• Do you refer your patients at high-risk for early relapse for CAR T prior to disease progression?

Sunn Sunn Thaw, MD: I am comfortable referring the patient. Typically, when the patient relapses, I usually consult with the cell therapy team to guide the therapy.

Priyanka Pophali, MD, MBBS: Do you ever refer your patients at high risk for early relapse for CAR T prior to disease progression?

Thaw: I have not. I treat it [with] first-line standard therapy, and then I monitor that.... Is there going to be any benefit doing that?

Pophali: I don't think so. The situation I'm thinking about is, if you don't have a clean PET scan at the end of treatment, if you have a Deauville score of 3, what would you do there?

Thaw: I have a case like that. I usually ask to consult with a lymphoma specialist. I found that they said to just wait for it, because some of those patients with diffuse large B-cell lymphoma remain [with] activity for some time. The subsequent scans cleared up. That was my experience, not that I was thinking about CAR T or anything like that; I just asked a question.

Pophali: I agree. Those are the hard ones where you don't have a clean PET scan. It's maybe in the same area where there was disease before, you can't tell whether it's inflammation, or it's in a mesenteric lymph node that you can't biopsy. In those cases, I think it's worth referring them just to get their foot in the door in case they need CAR T; that would be my thought. But if a patient is in remission, I don't necessarily believe that anyone with a high-grade B-cell lymphoma, even if it's double- or triple-hit lymphoma, needs a consultation early if they don't have any evidence of relapse or residual disease. I would say residual disease would be a situation where, prior to disease progression, you might consider referring a patient.

Thaw: I agree.

Balkrishna N. Jahagirdar, MBBS: How about transformed lymphoma? For example, if it's follicular lymphoma, you wouldn't always see a Deauville score of 1 or 2 right at the end of [treatment]…. After 4 cycles of, let's say, polatuzumab vedotin [Polivy], rituximab [Rituxan], cyclophosphamide, doxorubicin, and prednisone, you do a PET-CT scan, and there is still a Deauville score of 3 in certain areas. That's where I have seen it the most and those patients do [well] with ongoing therapy. Just like Dr Thaw experienced, I have seen complete responses at the end of 6 cycles.

Pophali: My advice there would be, it depends on the degree of partial response. It is such a broad term; you can have a Deauville score of 4 or 5, but it's a near complete response. If they had bulky disease of 10 cm and now it's a 3-cm mass, but it is avid on the PET scan, it's read as a Deauville score of 5. So I think it's a bit of a judgment call. You can't just go by the Deauville score.

Sometimes it depends on what degree of response you've had, what change in standardized uptake value and disease burden has occurred. But I think when you are worried or you have a positive scan, with a Deauville score of 3, 4, or 5, it's not incorrect to get your CAR T team involved, just in case it turns out that things don't go well for your patient, because things can progress rapidly and sometimes it's a challenge to time the [T-cell] collection and get things going for CAR T. In general, I wouldn't refer patients without evidence of residual disease or progression based on high-risk markers such as double- or triple-hit disease.

DISCUSSION QUESTIONS

• What are potential roadblocks encountered when referring your patients for CAR T-cell therapy?
• How do you view CAR T-cell therapy data compared with data for other options?

Pophali: If it's too much of an inconvenience for a patient to get a CAR T consult, are you more likely to now offer them bispecific treatment, and forego even the CAR T consult, or do you feel like it's still important?

Jahagirdar: I have always referred patients for CAR T-cell therapy. I practice close to the metro area, so most of the time, it's more or less one and done, although the patients have to live within—even for the bispecific antibodies—they have to live within a certain distance from the center where we are administering it for a certain amount of time to make sure they don't develop [adverse events] when we are doing the outpatient component of the ramp-up dosing.

I would say that I don't see any roadblocks in referring the patient for CAR T cells. The main attraction is it is one and done. Also, the long-term efficacy is much higher. It's not convenient for patients to come frequently for the bispecific antibody therapies, and especially with epcoritamab [Epkinly], where the therapy continues beyond a year. In the salvage setting, there are data on using the bispecific antibodies following CAR T-cell therapy. Vice versa is true, but then you need to use it in a smaller number of patients anyway.

Shahid Shekhani, MD: I agree. In past, when we dealt with clinical trials going on, there were very limited spots available. But in the last couple of years at least, it's become much easier to get a patient to CAR T. I think the only roadblock that we see is a patient factor rather than an institution factor. [If] the patient doesn't want to go, they cannot go, or they don't feel comfortable traveling, that is the only roadblock I've seen. But personally, I've not seen any concern from the institution to get the patient in.

Gordon J. Ruan, MD: I am still a bit nervous on the long-term follow-up data for the bispecific antibodies. If they get into a complete response, we would consider that a cure at my previous institution. Relapse after CAR T had a good response with bispecific and [if they're] young enough, we could be using that as a bridge to allogeneic transplant.

I'm still nervous with the data right now. I'd like to see more long-term follow-up data on if patients can be potentially cured with a bispecific antibody combination with chemotherapy. Right now, I would tell the patients that they're in remission, but I still worry that they would relapse at some point.

DISCLOSURES: Pophali previously reported receiving honoraria from SeaGen and an advisory board role with SeaGen, ADC therapeutics, Genentech, and Abbvie.