Interim Phase II ZUMA-5 Results Show Promise for Axi-Cel in R/R iNHL

Results showed that axicabtagene ciloleucel demonstrated significant and durable clinical benefit in patients with relapsed or refractory indolent non-Hodgkin lymphoma.

Results from an interim analysis of the phase II ZUMA-5 study showed that axicabtagene ciloleucel (axi-cel; Yescarta) demonstrated significant and durable clinical benefit, with high rates of overall response rate (ORR) and complete response (CR) observed, as well as a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma.1

The results, presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Meeting, indicate that axi-cel may be a promising approach for treating this patient population according to the investigators. 

“Advanced-stage indolent B-cell non-Hodgkin lymphomas are largely incurable with conventional therapies, with many patients experiencing multiple relapses over the natural history of their disease and remission shortening with subsequent therapies,” Caron A. Jacobson, MD, of the Dana-Farber Cancer Institute, said during a presentation of the data. 

Adults with relapsed or refractory follicular lymphoma (FL; grades 1-3a) and marginal zone lymphoma (MZL; nodal or extranodal) after ≥2 lines of therapy (including an anti-CD20 monoclonal antibody [mAb] with an alkylating agent), and an ECOG status of 0 or 1 were eligible for the study. Participants were leukapheresed and received conditioning chemotherapy followed by axi-cel infusion at 2 × 106 CAR T-cells/kg.

The primary endpoint of the study was objective response rate (ORR) by central review. Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and blood levels of cytokines and CAR T-cells.

As of December 16, 2019, 140 patients (FL, n= 124; MZL, n = 16) had received axi-cel with a median follow-up of 15.3 months (range, 1.9-28.8).

Of the 96 patients evaluable for efficacy, the ORR was 93% (95% CI, 86-97) and the complete response (CR) rate was 80% (95% CI, 71-88). The median time to first response was 1 month (range, 0.8-3.1). More specifically, patients with FL (n = 80) had an ORR of 95%, with an 81% CR rate, and those with MZL (n = 16) had an ORR of 81%, with a 75% CR rate. 

With a median follow-up of 15.3 months, the estimated DOR in all patients was 20.8 months, and 68% of patients with FL had an ongoing response as of the data cut-off. Moreover, the median PFS was 23.5 months (95% CI, 22.8 - NE) in all patients, and the median OS was not reached. However, the 12-months OS rate was 94.3% (95% CI, 86.8-97.6) for all patients. 

All of the study participants were evaluable for safety, and 119 patients (85%) experienced grade ≥ 3 adverse events (AEs). The most commonly observed AEs were neutropenia (34%) and anemia (22%). Additionally, grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 8% and 17% of patients, respectively. There were only 2 grade 5 AEs, including multisystem organ failure in the context of CRS (related to axi-cel) and aortic dissection (unrelated to axi-cel). 

“Given the long natural history of these diseases, safety is of paramount importance,” Jacobson said. “The safety profile was manageable and reversible, and appeared to be at least similar to that of axi-cel in aggressive lymphomas.”

The median time to peak of anti-CD19 CAR T-cell levels after axi-cel infusion was 8 days (range, 8 - 371). Furthermore, anti-CD19 CAR T-cells were detectable at 18 months in most patients with evaluable samples (13/15 [87%]).

“Axi-cel appears to be a promising therapeutic approach for patients with relapsed and refractory indolent B-cell non-Hodgkin lymphoma,” said Jacobson.

Axi-cel is currently approved by the FDA as a treatment for adult patients with relapsed or refractory large B-cell lymphoma based on findings from the phase II ZUMA-1 trial.2 The agent is indicated specifically following 2 prior therapies for those with diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma (TFL).


1. Jacobson CA, Chavez JC, Sehgal AR, et al. Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL). Presented at: 2020 ASCO Virtual Scientific Meeting; May 29, 2020. Abstract 8008.

2. FDA. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. FDA website. Published October 18, 2017. Accessed May 30, 2020.