The Curative Potential of Liso-Cel in Third-Line R/R LBCL

Manali Kamdar, MD

Jeremy S. Abramson, MD, the director of the Lymphoma Program and the Jon and Jo Ann Hagler Chair in Lymphoma at the Massachusetts General Hospital Cancer Center, recently presented 5-year survival data from patients treated in the LBCL cohort in TRANSCEND-NHL-001 clinical trial (NCT02631044) at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024. TRANSCEND-NHL-001 is evaluating Bristol Myers Squibb’s lisocabtagene maraleucel (liso-cel, marketed as Breyanzi), an autologous FDA-approved CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of third-line relapsed/refractory (r/r) large B-cell lymphoma (LBCL).

Shortly after the conference, CGTLive® interviewed Manali Kamdar, MD, the associate professor of medicine–hematology and clinical director of lymphoma services at the University of Colorado, to learn more. She went over the key findings and discussed their implications for the field.

CGTLive: Can you give an overview of the key results that were presented?

Manali Kamdar, MD, PhD: I guess let's start with the TRANSCEND-NHL-001 5-year follow up that was presented by Dr. Jeremy Abramson, MD, on behalf of the other coinvestigators. Just so that I can give a brief summary to the audience, the TRANSCEND-NHL-001 study is a multicenter, seamless design, pivotal study that investigated liso-cel in patients with r/r diffuse LBCL in the third line and higher settings. It showed an excellent overall response rate at 73% and a complete response rate of 53% with a very manageable safety profile, namely low incidence of grade 3 or higher cytokine release at 2% and neurological events at 10%. Based on these results, the FDA approved liso-cel as one of the CAR T-cell therapies that could be utilized in the third line setting. Now in the 2 year follow up of the TRANSCEND-NHL-001 study liso-cel showed durable remissions, which was a median duration of response of 23.1 months with no new safety signals. As everyone knows in the world of diffuse LBCL, we eagerly await the 5 year follow-up because patients who remain in a remission at the 5 year mark after diffuse LBCL treatment typically are considered to be cured.

So with that, Dr. Abramson presented the 5-year survival results in the LBCL cohort of the TRANSCEND-NHL-001 study. The net is that in this study, the median overall survival at the 5 year mark was 27.5 months, the estimated overall survival rate at 5 years was 38%, and the median disease-specific survival was 68 months with an estimated disease-specific survival rate at 5 years of 52%. These results underscore the curative potential of liso-cel in patients with r/r LBCL in the third line setting. Moreso over, there were no new safety signals that were seen clearly based on the recent FDA information. We are also very keen to look at second primary malignancies, and at this point in a cohort of 249 patients that were the liso-cel treated set, only 8% of patients had second primary malignancies, of which 4% had myelodysplastic syndrome. There were no patients with T-cell lymphoma. Most common second primary malignancies like I mentioned were either myelodysplastic syndrome or nonmelanoma skin cancers. Liso-cel persistence was also found. It was present in the peripheral blood in 34% of patients, with samples that were available at 5 years after infusion. So in conclusion of the 138 patients from the TRANSCEND study who were alive and. had received liso-cel and were eligible for the long-term follow up, 88 patients enrolled in the long-term follow up study. Among patients in the liso-cel-treated efficacy set, which was a total of 257 patients, the median overall survival was 28 months and the 5 year overall survival rate was 38%. Most deaths occurred before 2 years, suggesting that patients who are alive after 2 years had increased chances of prolonged survival. The liso-cel transgene continued to be detectable in 1/3 of patients in the evaluable samples, and overall, these data support the curative potential of liso-cel in patients in the third line setting with r/r LBCL.

What would you say are the big picture implications that doctors should take away from these findings?

In the third line setting, we clearly have CAR T-cell therapy as a standard that a lot of physicians implement in the management of patients who have had 2 or more lines of treatment and have progressed with their diffuse LBCL. We so far have 3 constructs that are approved, namely tisagenlecleucel, axicabtagene ciloleucel, and now liso-cel. All 3 have been approved for a while, and we do have 5 year follow-up data with axi-cel cell and tisa-cel, which was roughly 30% to 40% in the third-line setting. This goes on to show that liso-cel also demonstrates a curative potential of 38% at the 5 year mark in the patients who have received liso-cel in the third line setting. I think more importantly to focus on is the fact that in terms of toxicities, it is definitely much safer with regards to the incidence of high grade CRS and neurotoxicity. In terms of follow-up results, we see no new toxicity signals and as is true of any patient with a lot of pretreatment with chemo, as well as other treatments, the incidence of second primary malignancies is expected, but it's not high. It's less than 10%. That would be how I would summarize the data.

This transcript has been edited for clarity.

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REFERENCE
Abramson JS, Palomba ML, Gordon LI, et al. Five-year survival of patients (pts) from Transcend NHL 001 (TRANSCEND) supports curative potential of lisocabtagene maraleucel (liso-cel) in relapsed or refractory (r/r) large B-cell lymphoma (LBCL). Presented at: ASH 2024 Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract 3125