Leo I. Gordon, MD, on New Findings on Lisocabtagene Maraleucel for Large B-Cell Lymphoma
Posted: Tuesday, July 26, 2022
Leo I. Gordon, MD, of the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, discusses outcomes from the phase II PILOT study, which showed that lisocabtagene maraleucel, a CAR T-cell product, may have improved fatigue and FACT-LymS scores without negatively impacting other quality-of-life measures in patients with relapsed or refractory large B-cell lymphoma. The data also suggest that lisocabtagene maraleucel may become a new second-line treatment for patients not indicated for hematopoietic stem cell transplantation.
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Recent studies, the ZUMA-7 study, the TRANSFORM study, and the BELINDA study all address the question of how to approach patients with diffuse large B-cell lymphoma who relapse within 12 months of their initial remission, or who never achieve remission. And two of those studies, ZUMA-7 and TRANSFORM, suggested that CAR T therapy over autologous stem cell transplant, which is the previous standard, provides a better event free survival, and with data trending toward a better overall survival. The BELINDA study, which looked at Tisagenlecleucel or Kymriah, really didn't show a difference. But the other two, Zuma-7 with axi-cel and Transform with liso-cel both showed an improvement. So the question remained what to do with patients who relapsed, not within 12 months, but later on two years, three years, four years, but because of a number of comorbidities are not considered to be good candidates for an autologous stem cell transplant. So the pilot study addressed that particular issue. And what we looked at was a group of patients who were either over the age of 70, or who had renal dysfunction or cardiac dysfunction or pulmonary dysfunction. And because of that were not considered to be ideal candidates for an autologous transplant. This is a phase two trial, looking at liso-cel or brionze as therapy instead of a transplant. Now one of the questions is, what makes patients non candidates for transplant? It's a hard question. It's a bit of a moving target. We know that in some institutions, including ours, patients in their eighties have had auto autologous transplant. So I think this study doesn't necessarily rule out the possibility of a transplant, but it at least raises the question, is there something that can be done other than an auto autologous stem cell transplant? So we looked at 74 patients that were entered onto the trial. 61 of them actually received the liso-cel and the numbers that didn't, didn't for a number of reasons. They became ineligible, they withdrew, there might have been manufacturing issues. But if you look at the data, the overall response rate was 80% and the complete response rate was 54%. The median duration of response was over 12 months and for complete responders, the median duration of response was over 21 months. The median progression-free survival was about nine months and for complete responders was about 22 months. So I think what we see in this study, if you look also at the toxicity, which was very similar to the data from TRANSFORM and using liso-cel and to ZUMA-7 a seven using axi-cel with grade one, two, and very rare grade three cytokine release syndrome. And mostly grade one and two with very few grade three neurological toxicity. So I think when you look as a whole in this group of patients, the pilot study has raised the issue that for patients who may not be perfect candidates for transplant, but relapse with diffuse large b-cell lymphoma, that is in the second line, that on that CAR T therapy may be a viable option. And based on the data from this trial and also from the TRANSFORM trial and the ZUMA-7 trial, the FDA has approved both axi-cel and liso-cel for patients who relapsed within 12 months, but liso-cel, as of June 24th, 2022, liso-cel is now approved for anyone with large cell lymphoma who relapses but is not considered a good candidate for transplant. So I think an important advance and an important milestone for patients with this disease who relapse.