Jason Westin, MD, MD Anderson Cancer Center, Houston, Texas, discussed how the standard of care treatment for early relapsed large B-cell lymphoma shifted to CAR T-cell therapy, specifically axicabtagene ciloleucel or lisocabtagene maraleucel in the second line.

These insights and data were presented at the 2024 Pan Pacific Lymphoma (PPL) Conference in Lahaina, Hawaii.

Transcript:

Hi, my name is Dr. Jason Westin from MD Anderson Cancer Center in Houston, Texas. I'm here today to share with you the presentation I gave at the 2024 Pan Pacific Lymphoma Conference entitled "Early Relapsing Large B-cell Lymphoma CAR T-cell Therapy."

We've learned a lot over the past years about how to treat patients with large B-cell lymphoma and thankfully [with] frontline treatments [and] patients with newly diagnosed disease, treatments have gotten better. Therefore, there [are] less patients that are having relapsed large B-cell lymphoma.

Unfortunately, about a third of patients still suffer the fate of having their cancer come back after initial treatment for large B-cell lymphoma. And what we've learned most specifically over the past few years is that CAR T-cell therapy is the best treatment option for most patients in that situation. Historically, stem cell transplant, if high-dose chemotherapy had worked well, was the preferred standard for about 30 years.

But most recently, we've seen the ZUMA-7 and TRANSFORM phase 3 clinical trials, randomized patients to either the prior standard of care, or to (axicabtagene ciloleucel) axi-cel in ZUMA-7 or (lisocabtagene maraleucel) liso-cel in TRANSFORM, both of which showed superior event-free survival to the previous standard of care. Axi-cel showed statistically significant overall survival compared to the previous standard of care. Therefore, the paradigm has changed for most patients to now receive second-line CAR T-cell therapy.

If bridging treatment is required because of disease symptoms, that's okay, but the intention should still be to try to get a CAR T-cell therapy. Currently in the [United States] in 2024, the majority of patients who could benefit from CAR T-cell therapy are still not receiving this treatment and that's due to many reasons, but largely due to lack of knowledge about CAR T-cell therapy being superior and due to lack of access, [such as] patients not living near or being treated at a CAR T-cell center.

Doctors in the community should know that referring a patient early, if you suspect a patient has relapsed large B-cell lymphoma within the first 12 months after initial treatment, that's the time to make the referral to a center that does CAR T-cell therapy, not after you've given a couple of cycles of chemotherapy and then are considering what to do next. The reason for that is that the chemotherapy first and CAR T-cell later effectively was the control arm in the ZUMA-7 and TRANSFORM clinical trials, and that was inferior on all measures in terms of outcomes that would benefit our patients. So, the best treatment for patients with early relapsing large B-cell lymphoma is now to proceed directly to CAR T-cell therapy, specifically axi-cel or liso-cel, in the second line.

Dr Laurie Sehn and I published a review paper in [the journal] Blood entitled "A Paradigm Shift in Treatment of Large B-Cell Lymphoma" in 2022 detailing a new algorithm which effectively says that the old algorithm of stem cell transplant where half the patients could receive it, half the patients will be deemed transplant-ineligible, that's now out. The new algorithm saying that CAR T-cells are preferred and that about 70 % of patients could benefit from CAR T-cells, that’s in. That's what we think that we are now able to achieve is more patients receiving curative intent therapy.

There were 2 studies that were published in the last few years looking at patients who are transplant-ineligible, historically not fit to receive high-dose chemo[therapy] and transplant, but in these studies, they received CAR T-cell therapy. That was the pilot study with liso-cel or ALYCANTE with axi-cel. In both of those trials, patients even up into their late 80s were able to receive CAR T-cell therapy and have outcomes look very similar to what we saw for the younger population. Toxicity and efficacy seem very similar and therefore the pool of patients who are unable to receive a curative intent treatment in second line is dramatically smaller now that CAR T-cell therapy is the preferred approach.

In conclusion, we now know in 2024 that giving patients with early relapsed large B-cell lymphoma chemo[therapy] and transplant is no longer the standard of care. The new standard of care across the entire [United States] and across countries that have access to CAR T-cell is CAR T-cell therapy, specifically axi-cel or liso-cel. Thank you for your attention.

Source:

Westin J. Early Relapsing Large B-Cell Lymphoma - CAR-T Treatment. Presented at the 2024 Pan Pacific Lymphoma Conference. July 15–19, 2024; Lahaina, HI.