Tisagenlecleucel Approved in Europe for Relapsed/Refractory Follicular Lymphoma

The European Commission has approved the CD19-targeting chimeric antigen receptor (CAR) T-cell agent tisagenlecleucel (Kymriah) for the treatment of adults with relapsed/refractory follicular lymphoma following at least 2 lines of systemic therapy.¹

This marks the first time the European Medicines Agency (EMA) has approved a CAR T-cell therapy for this patient population, which includes those with grades 1, 2, and 3A disease .

The approval makes tisagenlecleucel now available to patients in the 27-member European Union along with Iceland, Norway, and Liechtenstein.

“When [follicular lymphoma] fails to respond to treatment or comes back, it is typically more aggressive and difficult to treat—patients often end up cycling through multiple lines of therapy with decreasing benefit,” Catherine Thieblemont, MD, PhD, professor of hematology in the Paris VII- University, France, and head of the hemato-oncology unit of St-Louis Hospital in Paris, said in a news release. “The approval of Kymriah in Europe brings patients closer to a potentially definitive therapy, providing us hope for improved outcomes.”

The EMA based its decision on data from the phase 2 ELARA trial (NCT03568461), in which tisagenlecleucel induced an objective response rate of 86.2% (95% CI, 77.5%-92.4%) with a complete response (CR) rate of 69.1% (95% CI, 58.8%-78.3%).

In findings from an extended follow-up analysis presented at the 2021 ASH Annual Meeting and Exposition, tisagenlecleucel induced a progression-free survival (PFS) rate of 67.0% (95% CI, 56.0%-75.8%) at 12 months.³ The 9-month duration of response (DOR) rate was 76.0% (95% CI, 64.6%-84.2%).

Among patients who had a CR, the 12-month PFS rate was 85.5% (95% CI, 74%-92%) and the estimated 9-month DOR rate was 86.5% (95% CI, 75%-93%). The median follow-up was 17 months (range, 10-26).

The median PFS was 29.5 months (95% CI, 17.9 to not evaluable) when evaluated a longer follow-up of 21 month.

Investigators recruited 98 adults into the single-arm, international trial. Eligible patients were diagnosed with relapsed/refractory grade 1, 2, or 3A follicular lymphoma. Patients were ineligible if they had evidence histological transformation, received anti-CD19 therapy, or underwent allogeneic hematopoietic stem cell transplant.

Patients underwent a screening period that included apheresis and cryopreservation, then received lymphodepletion chemotherapy. They then received CAR T-cell therapy doses from 0.6 x 108 cells to 6.0 x 108 cells.⁴

As of March 2021, 97 patients had received tisagenlecleucel. Ninety-four patients were evaluated for efficacy.²

The EMA previously approved tisagenlecleucel for children and young adults up to age 25 years with relapsed/refractory B-cell acute lymphoblastic leukemia following at least 2 lines of systemic therapy or stem cell transplantation and for adults with relapsed/refractory diffuse large B-cell lymphoma following at least 2 lines of systemic therapy.⁴

In October 2021, the FDA issued a priority review to tisagenlecleucel for adults with relapsed/refractory FL based on findings from ELARA. The regulatory agency also accepted a Type II Variation for the use of the CAR T-cell product in patients with relapsed/refractory follicular lymphoma following 2 prior lines of treatment.⁵

References

1. Novartis Kymriah receives EC approval as first CAR-T cell therapy for adults with relapsed or refractory follicular lymphoma. News release. Novartis. May 4, 2022. Accessed May 17, 2022. https://bit.ly/3yK5qY8
2. Fowler NH, Dickinson M, Dreyling M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med. 2022 Feb;28(2):325-332. doi:10.1038/s41591-021-01622-0
3. Thieblemont C, Dickinson M, Martinez-Lopez J, et al. Efficacy of tisagenlecleucel in adult patients (pts) with high-risk relapsed/refractory follicular lymphoma (r/r FL): subgroup analysis of the phase II ELARA study. Blood. 2021;138(suppl 1):131. 10.1182/blood-2021-145025
4. European Medicines Agency. Kymriah. Updated September 19, 2018. Accessed May 17, 2022. https://bit.ly/3sETJxQ
5. Novartis receives priority review by US FDA and filing acceptance by EMA for Kymriah to treat patients with relapsed or refractory follicular lymphoma. News release. Novartis. October 27, 2021. Accessed May 17, 2022. https://bit.ly/3jMIPla