The FDA has granted accelerated approval to tisagenlecleucel for the treatment of adult patients with relapsed/refractory follicular lymphoma after receiving 2 or more lines of systemic therapy.
The FDA has granted accelerated approval to tisagenlecleucel (Kymriah; tisa-cel) for the treatment of adult patients with relapsed/refractory (R/R) follicular lymphoma after receiving 2 or more lines of systemic therapy, according to Novartis.1
The basis of the approval comes from data concluded in the phase 2 ELARA trial (NCT03568461), examining tisagenlecleucel in this patient population. Findings revealed the trial to meet its primary end point as the CAR T-cell therapy produced an objective response rate (ORR) of 86.2%, with an independent review committee (IRC)–assessed complete response rate (CRR) of 66.0%.2 Further, robust responses were noted in heavily pretreated patients.
"We are proud of today's FDA approval of a third indication for [tisagenlecleucel'. We hope this treatment option that has the potential for long-lasting results may help break the unrelenting cycle of treatment for patients with follicular lymphoma," stated Victor Bulto, president of Novartis Innovative Medicines US, in the press release. "We are on a mission to build on our pioneering work in cell therapy and continue to innovate for patient impact."
ELARA is an open-label, single-arm, international study which evaluated patients with R/R follicular lymphoma. Those eligible for enrollment were adults aged 18 years or older with grade 1, 2, or 3A R/R follicular lymphoma which was radiographically measurable at the time of screening.3
Patients first underwent a screening period that included apheresis and cryopreservation. After enrolling to the trial, patients had the option to receive bridging chemotherapy as tisagenlecleucel was manufactured. This was followed by restaging and lymphodepletion chemotherapy, which could have comprised fludarabine at 25 mg/m2 daily for 3 days plus cyclophosphamide at 250 mg/m2 daily for 3 days or bendamustine at 90 mg/m2 daily for 2 days. Participants then received tisagenlecleucel at doses that ranged from 0.6 x 108 CAR-positive viable T cells to 6.0 x 108 cells.
Patients were administered tisagenlecleucel via a single intravenous (IV) infusion at a range of 0.6 to 6 x 106 of CAR-positive viable T cells. Lmphodepleting chemotherapy options consisted of fludarabine given at 25 mg/m2 IV daily for 3 days, plus cyclophosphamide at 250 mg/m2 IV daily for 2 days, or bendamustine at 90 mg/m2 daily for 2 days. Bridging therapy was allowed and followed by disease re-evaluation prior to tisagenlecleucel infusion.
The primary end point of the trial was CRR by IRC with secondary end points consisting of ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and cellular kinetics.
At the time of the data cutoff, September 28, 2020, a total of 98 patients were enrolled, and besides 1, all patients were infused with the CAR T-cell therapy. Those who received tisagenlecleucel were deemed to be evaluable for safety, and 94 patients were determined to be evaluable for efficacy and had at least 6 months of post-infusion follow-up.
For the 97 patients who were treated as well as the 94 patients in the efficacy set, the median follow-up was 10.6 months (range, 4.3-19.7) and 10.9 months (range, 4.3-19.7), respectively.
Data of ELARA trial which was presented during the 2021 ASCO Annual Meeting revealed that the median DOR had not yet been reached with tisagenlecleucel. Despite this, it was stated that the likelihood of a responding patient to remain in response after at least 6 months was 79% (95% CI, 66%-87%). Additionally, of the 31 partial responses seen (20.2%), 12 of them (38.7%) converted to complete responses between month 3 and month 6, with the exception of 1 patient.
The median time to next anti-lymphoma treatment was not reached, along with the median PFS (95% CI, 12.1–not evaluable [NE]) and the median OS (95% CI, NE–NE). However, the 6-month PFS rate was 76% (95% CI, 65%-84%).
A total of 99% of patients experienced any-grade adverse effects (AEs) when given the CAR T-cell product, 77.3% of which were suspected to be linked with tisagenlecleucel. Additionally, 41.2% of patients experienced a serious AE and 28.9% of them suspected to be related to the study drug. In regard to grade 3 or 4 AEs, 76.3% of patients reported them, with 45.4% of these effects thought to be drug related. Further, toxicities were managed by tocilizumab (Actemra) in 34% of patients and corticosteroids in 6.4%, and 3 deaths occurred on the trial, all of which were attributed to the study indication.
Grade 3 or greater cytokine release syndrome occurred in 48.5% vs 0% of treated patients, respectively, and all-grade and grade 3 or greater neurological adverse reactions occurred in 9.3% vs 1.0% of patients, respectively. The median onset for CRS was 4.0 days (range, 1-14) and all cases were low grade.