The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of tisagenlecleucel (Kymriah®, formerly CTL019) for 2 indications.

According to the CHMP, the chimeric antigen receptor (CAR) T-cell therapy should be approved to treat adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have received 2 or more lines of systemic therapy and patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

The CHMP’s recommendation will be reviewed by the European Commission, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The European Commission usually makes a decision within 67 days of the CHMP’s recommendation.

The CHMP’s recommendation is based on results from a pair of phase 2 trials—ELIANA and JULIET.

JULIET trial

Updated results from JULIET were presented at the recent 23rd Annual Congress of the European Hematology Association (EHA) as abstract S799.

The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so due to disease progression or clinical deterioration. The patients’ median age at baseline was 56 (range, 22-76).

Ninety-two percent of patients received bridging therapy, and 93% received lymphodepleting chemotherapy prior to tisagenlecleucel.

The median time from infusion to data cutoff was 13.9 months.

The overall response rate was 52%, and the complete response (CR) rate was 40%. Of the patients in CR at month 3, 83% remained in CR at month 12. The median duration of response was not reached.

At the time of data cutoff, none of the responders had proceeded to stem cell transplant.

For all infused patients (n=111), the 12-month overall survival (OS) rate was 49%, and the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome (CRS). Fifteen percent of patients received tocilizumab for CRS, including 3% of patients with grade 2 CRS and 50% of patients with grade 3 CRS.

Other adverse events (AEs) of interest included grade 3/4 neurologic events (12%), grade 3/4 cytopenias lasting more than 28 days (32%), grade 3/4 infections (20%), and grade 3/4 febrile neutropenia (15%).

ELIANA trial

Updated results from ELIANA were published in NEJM in February.

The trial included 75 children and young adults with relapsed/refractory ALL. The patients’ median age was 11 (range, 3 to 23).

All 75 patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The study’s primary endpoint was overall remission rate, which was defined as the rate of a best overall response of either CR or CR with incomplete hematologic recovery (CRi) within 3 months.

The overall remission rate was 81% (61/75), with 60% of patients (n=45) achieving a CR and 21% (n=16) achieving a CRi.

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to transplant while in remission. At last follow-up, 4 were still in remission, and 4 had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

All patients experienced at least 1 AE, and 95% had AEs thought to be related to tisagenlecleucel. The rate of grade 3/4 AEs was 88%, and the rate of related grade 3/4 AEs was 73%.

AEs of special interest included CRS (77%), neurologic events (40%), infections (43%), febrile neutropenia (35%), cytopenias not resolved by day 28 (37%), and tumor lysis syndrome (4%).

CHMP recommends CAR T for ALL, DLBCL