On 17 December 2021, Associate Professor Nathan Hale Fowler of Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center in Houston, TX, US and BostonGene in Waltham, MA, USA and ELARA colleagues published in the Nature Medicine the results from the primary, prespecified interim analysis of the phase II multinational study of tisagenlecleucel in adults with relapsed/refractory follicular lymphoma after two or more treatment lines or who relapsed after autologous stem cell transplant. Tisagenlecleucel was safe and effective in this extensively pretreated setting, including in high-risk patients. Professors Stephen J. Schuster of the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania in Philadelphia, PA, US and Catherine Thieblemont of the Hôpital Saint-Louis in Paris, France jointly supervised this work.
The authors wrote in the study background that follicular lymphoma is a common non-Hodgkin lymphoma that is generally considered indolent, but the disease remains incurable and the majority of patients eventually relapse. Although the median overall survival (OS) has improved with chemoimmunotherapy, approximately 20% of patients with follicular lymphoma experience progression of disease within 2 years of initial chemoimmunotherapy, and this subset of patients has a particularly poor prognosis. Patients with relapsed/refractory follicular lymphoma experience progressively shorter duration of response (DoR) to subsequent therapy as reflected by progression-free survival (PFS).
Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory B-cell lymphoma.
In a previous pilot study of tisagenlecleucel in relapsed/refractory follicular lymphoma, 71% of patients achieved a complete response (CR).
The ELARA investigators are now reporting the findings from the primary, prespecified interim analysis of their study of tisagenlecleucel in adults with relapsed/refractory follicular lymphoma after two or more treatment lines or who relapsed after autologous stem cell transplant. The study primary endpoint was CR rate. Secondary endpoints included overall response rate (ORR), DoR, PFS, OS, pharmaco-kinetics and safety.
The study team enrolled until 29 March 2021, 98 patients from whom 97 received tisagenlecleucel. Median follow-up was 16.59 months (interquartile range, 13.8–20.21 months).
The study primary endpoint was met. In the efficacy set comprised of 94 patients, CR rate was 69.1% (95% confidence interval [CI] 58.8–78.3) and ORR was 86.2% (95% CI 77.5–92.4).
In the safety set comprised of 97 patients, within 8 weeks of infusion rates of cytokine release syndrome were 48.5% with no grade ≥3. Neurological events were recorded in 37.1% of patients of whom 3% had a grade ≥3 and immune effector cell-associated neuro-toxicity syndrome was present in 4.1% of patients of whom 1% had grade ≥3. There were no treatment-related deaths.
The study team concluded that tisagenlecleucel is safe and effective in extensively pretreated relapsed/refractory follicular lymphoma, including in high-risk patients.
The study was sponsored and designed by Novartis Pharmaceuticals Corporation and was approved by the Institutional Review Board at each participating institution.
Fowler NH, Dickinson M, Dreyling M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nature Medicine; Published online 17 December 2021. DOI: https://doi.org/10.1038/s41591-021-01622-0