Early Relapsed DLBCL Requires Disease Control to Make CAR T Successful

Patients with early relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) are candidates for chimeric antigen receptor (CAR) T-cell therapy. Although it has demonstrated better outcomes for patients than alternative approaches, each patient’s unique needs may affect how and when they receive CAR T. In a Community Case Forum event in Los Angeles, California moderated by Ann F. Mohrbacher, MD, associate professor of clinical medicine at Keck Medicine of USC, the nuances of the available regimens for bridging to CAR were discussed. Additionally, Mohrbacher acknowledged the situations where patients may need to be treated with several cycles of therapy to fully control relapsed disease, and the cases where a patient may respond well enough to bridging to receive autologous stem cell transplant instead of CAR T-cell therapy.

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Targeted Oncology: What regimens can be used in DLBCL that is primary refractory or relapsed within 12 months?

Ann F. Mohrbacher, MD: Going to the NCCN guidelines for second-line therapy, clearly CAR T cells are at the top of the list: axicabtagene ciloleucel [axi-cel; Yescarta] or lisocabtagene maraleucel [liso-cel; Breyanzi] depending on frailty of the patient and the center that's treating.¹ We have bridging options. There's no right answer for that. In fact, everything we traditionally use to get someone ready for transplant would [impair] their T cells. If you could get permission to go to the CAR T track and get the T cells collected first, you can use almost any of those. It doesn't matter that much.

Bendamustine, though, has a very lingering effect on T cells across the board. We would prefer people forget pola-BR [polatuzumab vedotin (Polivy), bendamustine, and rituximab (Rituxan)] and just use pola-R if you want to give them something for bridging. That's one of the favorite bridging [regimens] to give. Polatuzumab is antibody targeted, but what you're delivering in the cells is chemotherapy, so you are giving a form of chemotherapy, and you can give it with rituximab as the second drug. People are [also] trying third-line combinations [as bridging].

You probably wouldn't do it if [polatuzumab was already used], and we're only now getting a number of people who would have had it in the first line. We haven't had that much before this. People are saying GemOx [gemcitabine plus oxaliplatin] is probably the least offensive of these drugs in terms of hitting T cells if you can't wait. I want to encourage that if you can get the T cells collected before you give anything, that would be optimal, but a lot of patients can't wait. The other thing is to remember radiation therapy if their disease is mostly confined to one area. The CAR T will clean up the rest. They're even looking at super-low–dose radiation for bridging…just to sensitize the T cells. None of these are optimal, but I want to cross bendamustine off the list. Think about radiation if it needs to be controlled in the local area.

What options could be used besides CAR T-cell therapy?

In terms of other options, we have bispecifics, either alone or with GemOx. We have pola-BR but I'd like people to still keep the bendamustine out of there, because if you're going to go into bispecifics, you still need your T cells. A lot of people are just doing pola-R, or nowadays you could look at one of the bispecifics with polatuzumab, if insurance lets you. Or you could do tafasitamab [Monjuvi] plus lenalidomide [Revlimid], which is FDA approved, a CD19 [antibody] plus lenalidomide, and, of course, all the old regimens we used to use. A new one that just came out is brentuximab vedotin [Adcetris]. Occasionally you have patients with B-cell lymphoma who are CD30 positive. It's not rare; make sure you ask your pathologist to check it.

Why is tafasitamab/lenalidomide excluded for primary refractory disease?

It's probably not enough. It's like giving R-squared [rituximab plus lenalidomide]. It doesn't have any direct cytotoxic in it. I probably wouldn't use it in a patient with primary refractory disease. In someone relapsed after a transplant…I've used it for that in older patients with relapse later, but they just don't have anything really cytotoxic in it. The lenalidomide is more helping the antibody-dependent cellular cytotoxicity. But for frail patients, [it’s an acceptable] thing to try. They didn't tend to take patients [with poor prognosis] onto the L-MIND study [NCT02399085]. They haven't proven it in a very refractory patient.

What are your thoughts on brentuximab plus R-squared?

It is recently approved [in the third line], but I don't think most people have even tried it yet. The approval just came out. I've used brentuximab a few times in patients with B-cell lymphoma. I think pathologists don't think to check CD30 on [DLBCL] relapses. I don't think single-agent brentuximab is very helpful. You'd probably need to combine it, but brentuximab is very combinable with other things. You can add it to anything. It's been combined with ICE [ifosfamide, carboplatin, and etoposide] and all sorts of other regimens [including] R-squared. An insurance company could say it's not FDA approved for [the second line]. There are nuances between second and third.

How do you address patients who need greater disease control after relapse?

[CAR T can] end up being the third line because you have to give another line of therapy controlling it. You have to give some second-line therapy in some of these patients. The problem is GemOx is the weakest choice of second-line therapy. I'd rather give them ICE or rituximab plus ICE. It depends on the patient. If you don't get that disease under control, the patient is not going to get to CAR T. It ends up being the third line. For a lot of patients, you don't have the luxury of waiting for a month of authorization.… They're sicker than that, so it ends up being the third line in a lot of these patients. Frankly…their T cells still usually survive 2 cycles of salvage chemotherapy.

But if they have a complete response, I switch them back to the transplant track. If they have a full response, transplant still has a higher cure rate. We have had people we thought were on the CAR T track, and we put them back on the transplant track when they had an excellent response to bridging. I realize you just have to pull out all the stops. I have a patient who I'm giving a second line of bridging in the middle, and I have to settle for radiation in the middle. Because of disease, they were going out. I've been fortunate that most insurers have been letting the radiation oncologists jump in there quickly because you [don’t want to] take too long.

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_{DISCLOSURES: There were no known relevant disclosures.}

_REFERENCE

_{1. NCCN. Clinical Practice Guidelines in Oncology. B-cell lymphomas, version 3.2025. Accessed September 25, 2025. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf}