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)
Authors: Abramson Jeremy S. , Palomba Maria Lia , Gordon Leo I. , Lunning Matthew , Wang Michael , Arnason Jon E. , Kamdar Manali , Maloney David G. , Shadman Mazyar , Andreadis Charalambos , Sehgal Alison R. , Solomon Scott R. , Ghosh Nilanjan , Hidalgo-López Juliana E. , Wang Jing , Ogasawara Ken , Singh Ashvin , Siddiqi Tanya 
Published: December 2024

Background: TRANSCEND (NCT02631044) demonstrated high ORR/CR rate with a manageable safety profile in R/R LBCL. At 2-y follow-up, liso-cel showed durable remissions (median duration of response [DOR], 23.1 mo) with no new safety signals (Abramson JS, et al. Blood 2024). In ZUMA-1, axicabtagene ciloleucel (axi-cel) showed a median OS of 25.8 mo with 5-y OS rate of 42.6% and 5-y disease-specific survival (DSS) rate of 51.0% (Neelapu SS, et al. Blood 2023). Here, we present 5-y survival results in the LBCL cohort of TRANSCEND, including data from the long-term follow-up (LTFU; NCT03435796) study.
Methods: Adult pts with R/R LBCL after ≥ 2 prior lines of systemic therapy were eligible. Bridging therapy was allowed and PET-positive disease was reconfirmed before lymphodepletion. Response was evaluated per Lugano 2014 criteria by independent review committee (IRC). Primary endpoints included AE rates and ORR. Liso-cel transgene levels were assessed in peripheral blood by qPCR (lower limit of detection, 5 copies/reaction).
Pts who completed the 2 y of study follow-up or who withdrew early could enroll in a separate LTFU study assessing safety and OS for up to 15 y after liso-cel; however, no IRC response assessments were performed in LTFU.
Results: Demographics and baseline characteristics for pts in the liso-cel-treated set (n = 270) were reported (Abramson JS, et al. Blood 2024). At the final TRANSCEND data cutoff (05/16/2024), 124 (46%) pts had completed the study and 146 (54%) had discontinued; 88 liso-cel-treated pts enrolled to LTFU. Median on-study follow-up (including LTFU) was 20.3 mo (range, 0.2-89.4). Liso-cel showed high response rates and durable remissions in the efficacy-evaluable set (n = 257) as observed at the 2-y follow-up with ORR of 73% (CR rate, 53%), median DOR of 23.1 mo (95% CI, 8.6-not reached [NR]), and median duration of CR of 26.1 mo (95% CI, 23.1-NR). Median PFS was 6.8 mo (95% CI, 3.3-12.7).
Median OS was 27.5 mo (95% CI, 16.2-47.3). Estimated 5-y OS rate was 38.1% (95% CI, 31.6%-44.7%). Six pts enrolled in the LTFU study were followed and alive at 7 y after infusion. Pts who achieved CR had prolonged OS (median [95% CI], NR [53.9-NR]) with 5-y OS rate of 55.9% (95% CI, 45.8%-64.9%). Estimated 5-y DSS rate (excluding deaths unrelated to disease progression) was 52.0% (95% CI, 45.1%-58.5%). Among the 345 leukapheresed pts, 175 (51%) died after CAR T cell infusion, with 136 (39%) deaths occurring &gt; 90 d after infusion, most commonly due to PD (n = 102; 30%). Thirty pts died &gt; 2 y after CAR T cell infusion, including 10 due to PD, 2 due to AEs (progressive multifocal leukoencephalopathy [PML] and COVID-19 pneumonia as noted below as grade 5 infections), 8 due to unknown reasons, and 10 due to other reasons, suggesting that most deaths occurred before 2 y and that pts who were alive at 2 y had increased chances of prolonged survival. Liso-cel was present in peripheral blood in 34% (13/38) of pts with samples available at 5 y after infusion.
Among the 249 pts with data in the post-TE period (≥ 91 d after liso-cel infusion or initiation of another anticancer therapy or liso-cel retreatment), no new safety signals were observed; 45% of pts had any-grade AEs and 25% had grade ≥ 3 AEs. The most common grade ≥ 3 post-TE AEs were cytopenias (neutropenia, 7%; anemia, 6%; thrombocytopenia, 4%). Median (range) duration of grade 3-4 prolonged (ie, unresolved at D29 visit) neutropenia, anemia, and thrombocytopenia was 26.5 d (3-337), 22.0 d (4-73), and 30.5 d (2-329), respectively. In the post-TE period, 14 (6%) pts had grade ≥ 3 infections (grade 5, n = 3). Of the 3 pts with grade 5 infections, 2 had received subsequent anticancer therapy; 1 died of septic shock on D79 after infusion and 5 d after subsequent anticancer therapy, 1 died of PML on D775 after infusion, and 1 died of COVID-19 pneumonia on D1660 after infusion and after subsequent anticancer therapy on D135. Nineteen (8%) pts had second primary malignancies (most commonly nonmelanoma skin cancers [n = 7] and myelodysplastic syndrome [n = 9]).
Conclusions: With longer follow-up, responses to liso-cel continue to be durable; the estimated OS rate at 5 y was 38.1% and estimated DSS rate at 5 y was 52.0%. Liso-cel showed similar median OS, 5-y OS rate, and 5-y DSS rate to those reported for ZUMA-1. Rates of grade ≥ 3 post-TE AEs were low, and no new safety signals were observed. These data support the curative potential of liso-cel in pts with R/R LBCL.