Braunschweig Makes the Case for Earlier Use of CAR T-Cell Therapy in DLBCL – OncLive

CAR T-cell therapy has shown robust responses and curative potential in patients with diffuse large B-cell lymphoma (DLBCL), regardless of cytogenetics or age, said Ira Braunschweig, MD, who added that the early use of tocilizumab (Actemra) and steroids has made it all the more likely that the modality could be moved to the up-front setting.

Its important to distinguish [between] the options a patient with aggressive lymphoma has, [particularly when it comes to] distinguishing between options that could help them versus options that can cure them, and CAR T-cell therapy stands alone as an option that could cure patients, said Braunschweig.

In an interview withOncLiveduring the 2020 Institutional Perspectives in Cancer webinar onhematologic malignancies, Braunschweig, director of the Stem Cell Transplant Program, clinical program director of Hematologic Malignancies at Montefiore Medical Center, and associate professor in the Department of Medicine (Oncology) at Albert Einstein College of Medicine, discussed the utility of CAR T-cell therapy in lymphoma and the rationale behind moving the modality to the up-front setting.

Braunschweig Its difficult to say, as far as efficacy, which [product] is better than the other because theyve never been compared head-to-head and probably never will be. It does seem that tisagenlecleucel [can be given as an] outpatient [therapy], which is nice.

Based on the data we have so far, we know that [these patients] respond very favorably [compared] with other subgroups. A [patient with] double hit or triple[-hit lymphoma] is not someone who will not respond [to the therapy], which is extremely encouraging.

We learned that axi-cel is as good as advertised, and [comparable with] what we saw on the clinical trial. Patients do not have to be in perfect condition to be able to tolerate and benefit from [the product], which is extremely importantnot every one of our patients is a marathon runner.

There was no difference between the older and younger populations [in terms of] response, which is also very encouraging, because we treat a lot of older patients. [Knowing] that [the product] is effective in that group [of patients] as well is great.

[CAR T-cell therapy is a fantastic option for] a [patient with] primary refractory or multiply relapsed [disease] or [a patient with] relapsed [disease] posttransplant. For a certain number of patients, [CAR T-cell therapy] will likely be a curative therapy. [CAR T-cell therapy] has been truly a game changer for these patients.

For a chemotherapy-sensitive patient, autologous transplant is still the standard of care, largely, in part because we have decades of experience with those patients. When we get to a primary refractory patient, it would seem that CAR T-cell therapy is the clear choice. Only a few years ago, we used to offer a [patient with] relapsed [disease] post-autologous transplant an allogeneic transplant, and there are data that that treatment could be curative for such a patient.

However, we have to recognize that there is a lot of graft-versus-host-disease and ongoing health issues [that accompany] allogeneic transplant. With CAR T-cell therapy, if [patients] get through the first couple of weeks of toxicities, theres a lot less of a concern about their long-term health. In fact, with CAR T-cell therapies, data are coming out that we can treat these toxicities effectively without worrying about abrogating the antitumor response, which makes it even more attractive.

There are data that early tocilizumab can, at the first fevers, abrogate the CRS toxicity without abrogating the antitumor effect. Even [early use of] steroids, which are lymphocyte killers, is supported by data for neurotoxicity and does not seem to abrogate the antitumor response. If we could [treat patients even] earlier [with these interventions] and not have them become confused, or [enter a certain coma level], that could be even better.

Once we know that its extremely effective for [patients with] relapsed/refractory [disease], and we know that its effective for [patients with] high-risk genetic genetics, perhaps we could offer those patients up-front CAR T-cell therapy after some cytoreduction with chemotherapy as a consolidation approach.

If we know a patient has a high risk of relapse, it makes perfect sense to offer [CAR T-cell therapy] to them up front. Its an effective therapy for those patients. If we know that theyre ultimately going to fail [treatment], then why wouldnt we [offer it to them up front? For those patients that could be cured with R-CHOP, R-CHOP is still probably the way to go. [Well have to] figure out whos not going to do well with R-CHOP [and may be a candidate for CAR T-cell therapy up front].

[Theres research evaluating] dual targets. Can we combine novel agents with CAR T-cell therapy to increase its effectiveness? Maybe well offer more than one infusion of CAR T-cell therapy. If so, there might be a tandem CAR T-cell therapy one day. Those things are being looked at.

The most important point is that a [patient with] multiply relapsed [or] even refractory lymphoma [should be considered for CAR T-cell therapy] as a curative option for treatment.

We have a robust CAR T-cell therapy unit. Weve treated the first [patient] in the nation with the FDA-approved [brexucabtagene autoleucel (Tecartus)] for mantle cell lymphoma with excellent results, and we have ongoing trials with CAR T-cell therapy in multiple myeloma as well.

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Braunschweig Makes the Case for Earlier Use of CAR T-Cell Therapy in DLBCL - OncLive

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