ZUMA-5: Axicabtagene Ciloleucel Induces High Response Rates in Relapsed/Refractory Indolent NHL

According to research presented at EHA2021 Virtual, the annual congress of the European Hematology Association, treatment with the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel) led to high response rates in patients with relapsed/refractory indolent non-Hodgkin lymphoma.

With the exception of progression-free survival (PFS) rates, efficacy results as well as safety and pharmacological profiles appeared comparable between patients with and without disease progression within 24 months of initiation of frontline anti-CD20–containing chemoimmunotherapy (POD24), said lead author and presenter Caron A. Jacobson, MD.

The phase II ZUMA-5 trial enrolled 129 adults with relapsed or refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL) who had received at least two prior lines of therapy. At baseline, 81 patients (63%) had POD24. In the POD24 group, 68 patients had FL, and 13 had MZL. Of the 48 patients without POD24, 40 had FL, while eight had MZL.

The median prior lines of therapy was three in the POD24 group and 3.5 in those without POD24. High-risk characteristics for patients with and without POD24, respectively, included:

  • stage III/IV disease (83% and 94%)
  • Follicular Lymphoma International Prognostic Index (FLIPI) score of ≥3 (44% and 43%)
  • high tumor bulk, per Groupe d’Etude des Lymphomes Folliculaires (GELF) criteria (51% and 44%)
  • refractory disease (77% and 63%)

Patients underwent leukapheresis followed by conditioning chemotherapy (consisting of 30 mg/m2 IV fludarabine and 500 mg/m2 IV cyclophosphamide) before receiving the CAR T-cell therapy. Axi-cel was delivered as an infusion of 2×106 CAR T cells/kg). An updated efficacy analysis was conducted when at least 80 patients with FL who received axi-cel had at least 18 months of follow-up data.

In both groups, the overall response rate was 92%. At a median follow-up of 17.1 months for patients with POD24 and 17.5 months for patients without, responses were ongoing for 52% of efficacy-evaluable patients with POD24 and 70% of those without. Overall survival was not reached in either group.

Although median PFS was not reached in either group, estimated PFS rates at 18 months appeared lower in the POD24 cohort (55% versus 84%). This discrepancy might be explained by “higher median pretreatment levels of analytes previously associated with relapse (CC17 and CCL22) in patients with POD24 than without POD24,” Dr. Jacobson noted.

In efficacy-evaluable patients with FL, median peak CAR T-cell levels for patients with POD24 were 35.8 cells/μL, compared with 34.5 cells/μL for patients without POD24. “Peak levels of key inflammatory biomarkers and axi-cel product attributes were generally similar in patients with and without POD24,” Dr. Jacobson commented.

Adverse events (AEs) were considered manageable across both groups, according to the study authors. Grade ≥3 AEs occurred in 84% and 88% of patients with and without POD24, respectively. These included cytopenias (69% and 65%) and infections (15% and 21%). In addition, 9% and 2% of patients with and without POD24 experienced grade ≥3 cytokine release syndrome, and grade ≥3 neurologic events occurred in 17% of patients in each group.

The authors report relationships with Kite, a Gilead Company, which funded the study.


Jacobson CA, Chavez JC, Sehgal AR. Outcomes in ZUMA-5 with axicabtagene ciloleucel in patients with relapsed/refractory indolent non-Hodgkin lymphoma who had the high-risk feature of early progression after first chemoimmunotherapy. Abstract #S213. Presented at the EHA2021 Virtual Congress, June 9-17, 2021.