CAR T-Cell Therapy in Relapsed/Refractory DLBCL: Lisocabtagene Maraleucel

Transcript:
Matthew A. Lunning, DO, FACP: Dr Saeed, we’ve talked a lot about axicabtagene-ciloleucel in the second line, but there was another CAR T cell in the second-line randomized setting in the TRANSFORM study. Talk a little about transform and lisocabtagene-maraleucel.

Hayder M. Saeed, MD: TRANSFORM was similar to ZUMA-7 in terms of design. It’s a randomized phase 3 trial comparing patients with relapsed/refractory—patients who relapsed within 12 months of their frontline therapy—diffuse large B-cell lymphoma. Patients were randomized to either standard of care that we had at that time, which was a chemotherapy platinum-based regimen. They allowed only 3 regimens in that study, which is R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin], R-GDP [rituximab, dexamethasone, gemcitabine], and R-ICE [rituximab, ifosfamide, etoposide], which are the largest 3 regimens we use in the second-line treatment of diffuse large B-cell lymphoma. Patients were randomized to that option or to lisocabtagene-maraleucel in relapsed/refractory setting. That was the other study published in the same ASH [American Society of Hematology Annual Meeting], and it showed improvement in event-free survival.

The follow-up on that study was a little shorter than ZUMA-7, but it was a positive study that showed event-free survival improvement of around 10 months vs 2 months on the chemotherapy arm. It replicated what we anticipated from the control arm in the relapsed/refractory setting of diffuse large B-cell lymphoma, which is that the chemotherapy option in those refractory patients is not good, and alternative therapy should be used.

There was also a follow-up. It’s hard to tell whether some of the challenges we’ve seen in the ZUMA-7—the comorbidities and age of the patient—are challenging to put them on the axicabtagene-ciloleucel. There was a follow-up population study between ZUMA-7 and TRANSFORM that looked at whether there was any difference between the patients on both studies. The outcome was relatively similar. However, lisocabtagene-maraleucel had a little better toxicity profile. In our clinical practice, if the patient has more comorbidities and a little older age, if we feel the CRS [cytokine release syndrome] toxicity or neurotoxicity might be a concerning, we might lean toward lisocabtagene-maraleucel over axicabtagene. However, there’s no real head-to-head comparison between those 2 CARs.

Matthew A. Lunning, DO, FACP: Very good. As Dr [Jason] Westin was saying, don’t hold back your axicabtagene-ciloleucel. Dr [Jeremy] Abramson presented data showing that we shouldn’t hold back on lisocabtagene-maraleucel too and wait for the third line.

Transcript edtied for clarity.