Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma

Abstract

The ELARA trial indicates tisagenlecleucel (tisa-cel) is an effective anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory follicular lymphoma (r/r FL). As ELARA is single-arm, this study compared tisa-cel outcomes from ELARA with usual care from a real-world cohort. ELARA enrolled 98 patients as of 29Mar2021 (median follow-up: 15 months from enrollment). Usual care data came from ReCORD-FL, a global retrospective study of r/r FL patients who met similar eligibility criteria to ELARA. With data cutoff of 31Dec2020, 187 patients with ≥2 prior treatment lines were included in ReCORD-FL (median follow-up: 57 months from third-line). Indirect treatment comparison was performed for 97 ELARA and 143 ReCORD-FL patients with no missing data on baseline factors. The line of therapy for which outcomes were assessed was selected/matched between cohorts using propensity score modeling. After baseline factor adjustment via weighting by odds, complete response rate (CRR; 95% confidence interval) was 69.1% (59.8%-78.3%) for tisa-cel vs. 37.3% (26.4%-48.3%) for usual care; overall response rate was 85.6% (78.7%-92.5%) vs. 63.6% (52.5%-74.7%). Kaplan-Meier probability of being progression/event-free at 12 months was 70.5% (61.4%-79.7%) for tisa-cel vs. 51.9% (40.6%-63.3%) for usual care, with hazard ratio (HR)=0.60 (0.34-0.86); 12-month overall survival was 96.6% (92.9%-100%) vs. 71.7% (61.2%-82.2%), with HR=0.2 (0.02-0.38). In conclusion, tisa-cel was associated with 1.9-fold higher CRR and 1.4-fold higher rate of being progression/event-free at 12 months versus usual care, as well as death risk reduction of 80%. Findings provide additional evidence on the benefit of tisa-cel in r/r FL patients after ≥2 treatment lines. This trial is registered at www.clinicaltrials.gov as NCT03568461.

Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update

“…These updated data are bolstered by recent findings from retrospective analyses (before mosunetuzumab) comparing ELARA with real-world evidence, demonstrating improved efficacy of tisagenlecleucel over other SOC options. 11 , 12 Patients from ELARA had an estimated 1.4-fold higher PFS rate at 12 months and an 80% reduction in risk of death compared with SOC. 11 Similarly, comparison of ELARA vs the US Flatiron Health Research Database indicated improved efficacy across CRR (69% vs 18%), 12-month PFS (73% vs 42%), OS (97% vs 85%), and TTNT (86% vs 52%) for tisagenlecleucel compared with SOC.…”

“… 11 , 12 Patients from ELARA had an estimated 1.4-fold higher PFS rate at 12 months and an 80% reduction in risk of death compared with SOC. 11 Similarly, comparison of ELARA vs the US Flatiron Health Research Database indicated improved efficacy across CRR (69% vs 18%), 12-month PFS (73% vs 42%), OS (97% vs 85%), and TTNT (86% vs 52%) for tisagenlecleucel compared with SOC. 12 These benefits over SOC were observed regardless of number of previous therapies, requirement for bridging therapy, or POD24 status.…”

“… 6 , 27 These findings are consistent with the homogeneous treatment effect seen in ELARA regardless of the number of prior lines of therapy, and demonstrates that patient outcomes were still superior to the current non–CAR T-cell therapy SOC. 11 , 28 , 29 , 30 , 31 , 32 , 33 , 34 Although difficulties with cross-trial comparisons and variation in follow-up duration between the studies limit definitive conclusions, the safety profile of tisagenlecleucel continues to compare favorably with that of axicabtagene ciloleucel. 26 Notably, both ZUMA-5 and the TRANSCEND-FL phase 2 trial allowed the use of bridging therapy at the discretion of the physician.…”

Chimeric Antigen Receptor-T Cell Therapy for Lymphoma: New Settings and Future Directions

“…Toxicities were seemingly lower than those of axi-cel, with no CRS exceeding grade 2 and grade ≥ 3 ICANS of 3% [ 31 ]. Again, a propensity score matching study confirmed the stronger efficacy of CAR-T cell therapy compared to usual care both in terms of PFS and OS [ 32 ].…”

T-Zell-rekrutierende Immuntherapien des B-Zell-Lymphoms – bald in allen Therapielinien?

“…In Anbetracht der Erkrankungskinetik von FL sind die Nachbeobachtungszeiten der Studien immer noch relativ kurz, zeigen jedoch langanhaltende Remissionen bei einem Teil der Patient*innen (mediane Remissionsdauer für Axi-cel 38,6 Monate, für Tisa-cel nicht erreicht [13,14]). Retrospektive Propensity-Score-gematchte Vergleiche mit historischen Kohorten deuten zudem auf eine bessere Wirksamkeit der CAR-T-Zell-Therapie im Vergleich zum bisherigen Therapiestandard hin [15,16] Merke Bispecifics stellen damit eine aussichtsreiche Therapiestrategie nach Versagen einer CD19-CAR-T-Zell-Therapie dar [20,21].…”