Durable Response After Tisagenlecleucel in Adults With Relapsed/Refractory Follicular Lymphoma: ELARA Trial Update.
Martin DreylingNathan H FowlerMichael J DickinsonJoaquín Martínez-LópezArne KolstadJason P ButlerMonalisa GhoshLeslie PopplewellJulio C ChavezEmmanuel BachyKoji KatoHideo HarigaeMarie José KerstenCharalambos Babis AndreadisPeter A RiedellP Joy HoJose Antonio Perez-SimonAndy I ChenLoretta J NastoupilBastian von TresckowAndrés José Maria FerreriTakanori TeshimaPiers E M PattenJoseph P McGuirkAndreas L PetzerFritz OffnerAndreas ViardotPier Luigi Luigi ZinzaniRam MalladiInes PauleAiesha ZiaRakesh AwasthiXia HanDavide GermanoDarragh Stephen O'DonovanRoberto Javier RamosHarald J MaierAisha MasoodCatherine ThieblemontStephen J SchusterPublished in: Blood (2024)
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.
Keyphrases
- phase ii
- stem cells
- clinical trial
- acute myeloid leukemia
- free survival
- acute lymphoblastic leukemia
- hodgkin lymphoma
- diffuse large b cell lymphoma
- randomized controlled trial
- study protocol
- low dose
- ejection fraction
- high resolution
- radiation therapy
- metabolic syndrome
- squamous cell carcinoma
- mass spectrometry
- bone marrow
- multidrug resistant
- preterm infants
- skeletal muscle
- type diabetes
- prognostic factors
- cell death
- locally advanced
- mesenchymal stem cells
- smoking cessation
- data analysis