In the phase 3 TRANSFORM study, CAR T cell product lisocabtagene maraleucel (liso-cel) demonstrated superiority over standard-of-care, with significant and clinically meaningful improvements in event-free survival (EFS), progression-free survival (PFS), and complete response (CR) rate as second-line therapy in patients with large B-cell lymphoma (LBCL) who were primary refractory to initial treatment or relapsed ≤1 year after first-line therapy . The Safety profile in the second-line setting was consistent with the liso-cel safety profile in the third-line or later. These results support the conclusion that liso-cel is a potential new standard-of-care for second-line treatment of this patient population, and provide broader implications in the application of CAR T-cell therapies in earlier lines of LBCL treatment.
Patients with LBCL who are refractory to first-line therapy or relapsed ≤1 year after first-line therapy initiation have poor outcomes with the current standard-of-care, consisting of salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) [2-4]. The 3-year EFS rates are approximately 20% for this treatment .
Previous studies with liso-cel
Liso-cel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell product administered at an equal target dose of CD8+ and CD4+ CAR-positive T cells. “In the phase 1 TRANSCEND NHL 001 study (NCT02631044), liso-cel has demonstrated excellent efficacy and manageable safety in patients with R/R LBCL after ≥2 prior lines of therapy,” said Dr Manali Kamdar (University of Colorado Cancer Center, Denver, USA). Liso-cel treatment resulted in an objective response rate (ORR) of 83%, with a CR rate of 53%. In addition, few grade ≥3 cytokine release syndrome (CRS) or neurological events were reported .
Liso-cel versus standard-of-care
Dr Kamdar presented a prespecified interim analysis of the phase 3 TRANSFORM study (NCT03575351) evaluating the efficacy and safety of liso-cel versus standard-of-care as second-line therapy in patients with R/R LBCL. The results showed that median EFS and median PFS were significantly longer in patients receiving liso-cel. Moreover, the CR rate was significantly higher in the liso-cel arm compared with the standard-of-care arm (see Table 1).
After a median follow-up of 6.2 months (range 0.9–20.0), median OS was not achieved. However, a numerical trend favoured the liso-cel arm over the standard-of-care arm (HR 0.509; 95% CI 0.258–1.004; P=0.0257).
Safety results in the second-line setting were consistent with the liso-cel safety profile in the third-line or later. No new safety signals of liso-cel were detected in the current study. In the liso-cel arm, any-grade CRS was reported in 49% of patients, with grade 1 in 37% and grade 2 in 11%. Only 1 patient experienced a grade 3 CRS event.
Any-grade neurological events were reported in 12% of the patients. These events were primarily low-grade events, with only 4% of the patients demonstrating a grade3 event. No grade 4 or 5 CRS or neurological events were reported.
In the TRANSFORM study, liso-cel demonstrated superiority over salvage chemotherapy followed by high-dose chemotherapy and ASCT (standard of care), with highly significant and clinically meaningful improvement in EFS, CR rate and PFS as second-line therapy in patients with LBCL primary refractory to or relapsed ≤1 year after first-line therapy. In addition to the improved outcomes, liso-cel exhibited a favourable safety profile.
- Kamdar M, et al. Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Versus Standard of Care (SOC) with Salvage Chemotherapy (CT) Followed By Autologous Stem Cell Transplantation (ASCT) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Randomized Phase 3 Transform Study. Abstract 91, ASH 2021 Annual Meeting, 11-14 Dec.
- Crump M, et al. J Clin Oncol. 2014;32:3490-6.
- van Imhoff GW, et al. J Clin Oncol. 2017;35:544-551.
- Gisselbrecht C, et al. J Clin Oncol. 2010;28:4184-90.
- Abramson JS, et al. Abstract 91, ASH 2021 Annual Meeting, 11-14 Dec.
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