Tisagenlecleucel: CAR-T cell therapy for adult patients with relapsed or refractory follicular lymphoma

ABSTRACTIntroduction Tisagenlecleucel (tisa-cel) is an anti CD19 CAR-T therapy that has demonstrated clinical activity in R/R large B-cell lymphoma and R/R B-cell acute lymphoblastic leukemia. It showed particularly high efficacy in R/R follicular lymphoma (FL) with a manageable toxicity profile. The pivotal ELARA study in R/R FL confirmed these findings and led to the FDA approval of tisa-cel in R/R FL after two lines of systemic therapies.Areas covered We start with an introduction of FL and the current treatment landscape with emphasis on the R/R setting. We review the role of CAR-T in R/R FL with focus on currently available products. We describe the ELARA study at a high level to give a perspective of the patient population that was treated. Finally, we discuss aspects related to product selection and whether bispecific antibodies will challenge the role of CAR-T in FL given their similar efficacy.Expert opinion Tisa-cel is a highly effective therapy for heavily pretreated R/R FL with a toxicity profile that is low grade and manageable. Durable remissions (including high-risk patients) are seen in the pivotal ELARA study. Clinicians should consider early referral of R/R FL patients for assessment and discussion.KEYWORDS: TisagenlecleucelCAR-Tfollicular lymphomaImmunitherapyRefractory Article highlights Tisagenlecleucel (tisa-cel) is an autologous anti-CD19 CAR-T therapy approved for R/R B-cell acute lymphoblastic leukemia, R/R large B-cell lymphoma, and R/R follicular lymphoma (FL).The pivotal ELARA study showed high response rates and durable remissions in heavily pretreated high-risk R/R FL.Tisa-cel was associated with CAR-T related toxicities such as cytokine release syndrome and immune cellular effector neurotoxicity syndrome, but they were mostly grade 1–2 and manageable with standard protocols.Long-term follow-up of earlier studies with tisa-cel shows durable remissions, and longer follow-up of the ELARA study is needed to confirm earlier findingsEarly referral for CAR-T therapy for R/R FL is recommended, especially in high-risk cases.Declaration of interestJC Chavez has acted as a consultant for Kite/Gilead, Novartis, GenMab, BMS, Genentech, AstraZeneca, and TeneBio. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Company reviewNovartis provided a scientific accuracy review at the request of the journal editor.Additional informationFundingThis paper was not funded.