KEY TAKEAWAYS
- The Phase II ELARA study aimed to assess the long-term clinical outcomes and correlative efficacy of tisagenlecleucel in pts with R/R FL.
- The study’s primary endpoint was CR.
- The trial revealed that tisagenlecleucel offers high efficacy and a commendable safety record for adults with R/R FL.
Tisagenlecleucel became the first CAR-T-cell therapy to receive approval in both the US and the EU for Relapsed/Refractory Follicular Lymphoma (R/R FL) patients (pts) who have undergone at least 2 previous treatments. The primary analysis from the Phase II ELARA trial – a single-arm, open-label study – showed that tisagenlecleucel provided high efficacy and a good safety record for R/R FL adult pts.
The study’s objective was to assess the continued durability of response, longer-term safety, biomarkers, and pharmacokinetics after over two years of follow-up.
Participants included those diagnosed with grade 1-3A R/R FL who had undergone two or more treatment lines or had a relapse after an autologous stem cell transplant. Administering bridging chemotherapy was allowed. Patients were given a single dose of tisagenlecleucel (0.6-6×108 CAR + live T-cells) post-lymphodepleting chemotherapy.
The primary endpoint was the rate of complete response (CR). Factors like clinical response, progression-free survival (PFS), correlation with baseline elements, tumor microenvironment (TME), soluble factors, and circulating blood cells were considered. Cellular kinetics were identified using quantitative polymerase chain reaction to measure transgene levels.
Of 94 assessable pts (with a median follow-up of 28.9 months), 68% displayed a CR rate, and the overall response rate stood at 86.2%. The median PFS hasn’t been achieved yet. The estimated 24-month PFS, duration of response, and overall survival were 57.4%, 64.6%, and 87.7%, respectively. No new safety concerns arose. 12 pts (12.3%) experienced neurological events, with one possibly having progressive multifocal leukoencephalopathy after previously experiencing a severe immune effector cell-associated neurotoxicity syndrome. Three new deaths occurred during extended follow-up, but none were linked to the treatment. Transgene lasted an average of 210 days. High initial tumor load, disease progression within two years of the first chemoimmunotherapy, and presence in over 4 nodal areas at the start significantly aligned with reduced efficacy. A reduced inflammatory state, characterized by lower IL-10 and TNF-α levels and fewer LAG3+ exhausted T-cells in the tumor environment, were linked with extended PFS.
The ELARA trial confirmed that tisagenlecleucel remains a safe and effective option for R/R FL pts, including those with high-risk disease traits. Favorable TME and reduced inflammation may contribute to better results.
Source: https://clml-soho2023.elsevierdigitaledition.com/534/index.html
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03568461
Fowler, N., Dreyling, M., Dickinson, M., Martinez-Lopez, J., Kolstad, A., Butler, J., Ghosh, M., Popplewell, L., Chavez, J., Bachy, E., Kato, K., Harigae, H., Kersten, M. J., Andreadis, C., Riedell, P., Ho, P. J., Pérez-Simón, J. A., Chen, A., Nastoupil, L., Tresckow, B.V., Ferreri, A.J.M., Teshima, T., Patten, P., McGuirk, J., Petzer, A., Offner, F., Viardot, A., Zinzani, P., Malladi, R., Paule, I., Zia, A., Awasthi, R., Han, X., Germano, D., O’Donovan, D., Ramos, R., Masood, A., Thieblemont, C., Schuster, S. (2023). CT-564 ELARA Trial Update: Long-Term Clinical Outcomes and Correlative Efficacy Analyses of Tisagenlecleucel in Patients With Relapsed/Refractory Follicular Lymphoma (R/R FL). Clinical Lymphoma Myeloma and Leukemia, 23, S534-S535. https://doi.org/10.1016/S2152-2650(23)01523-9
