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

Abstract

Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the ≥3rd-line setting. The primary analysis (median follow-up: 17 months) of the Phase II ELARA trial (ClinicalTrials.gov identifier: NCT03568461) reported high response rates and excellent safety profile in extensively pretreated patients with r/r FL. Here we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after a median follow-up of 29 months. As of March 29, 2022, 97 patients with r/r FL (grades 1-3A) after ≥2 lines of therapy or who relapsed after autologous stem cell transplant received tisagenlecleucel infusion (0.6-6×108 CAR+ viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment (TME), blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached after 29 months median follow-up (IQR, 22.2-37.7). Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% CI, 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2). Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T-cells and higher baseline levels of naïve CD8+ T-cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA.

Late events after anti-CD19 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma

“…The prevalence of G3/4 cytopenia at D90 was 26% in the pivotal trial of brexucabtagene autoleucel (brexu-cel) for R/R mantle cell lymphoma (MCL), and in the RWE, the prevalence of G3/4 neutropenia and thrombocytopenia at D90 was 18% and 11%, respectively. In pivotal trials of CART19 for R/R follicular lymphoma (FL), the prevalence of D90 G3/4 cytopenia was 6% with axi-cel, and the probability of G3/4 cytopenia at 6 months was 18% with tisa-cel ( Table 1 ) ( 1 , 7 , 11 , 23 – 25 , 30 ).…”

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

“…Basis der Zulassungen durch EMA und FDA für beide Präparate waren einarmige Studien, die eine gute Wirksamkeit der Therapie mit Ansprechraten > 80 % und Vollremissionen in >⅔ aller behandelten Patienten zeigten. 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].…”

Effectiveness of CAR-T treatment toward the potential risk of second malignancies

“…The primary analysis of the Phase II ELARA trial reported high response rates and excellent safety profile in extensively pretreated patients with r/r FL ( 44 ). Findings from a longer-term update of the ELARA trial continue to demonstrate high response rates and durable remissions with a favorable safety profile ( 45 ). No new safety signals were reported.…”