All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.

The Lymphoma Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

An expert panel hosted by

The Lymphoma Hub logo and the Multiple Myeloma Hub logo

Sequencing immune-based therapies in B-cell malignancies

with Ulric Jäger, Sagar Lonial, and Krina Patel

Saturday, June 15 | 18:00-19:30 CEST

Register now

This independent education activity is sponsored by Bristol Myers Squibb. All content is developed independently by the faculty. Funders are allowed no direct influence on the content of this activity.


The Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact
You're logged in! Click here any time to manage your account or log out.
You're logged in! Click here any time to manage your account or log out.

ZUMA-12 primary analysis: Axi-cel for the frontline treatment for high-risk LBCL

Apr 21, 2022
Learning objective: After reading this article, learners will be able to cite a new clinical development in lymphoma/CLL

The CAR T-cell product axicabtagene ciloleucel (axi-cel) has become established as a successful treatment for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The efficacy and safety of axi-cel as a frontline treatment for high-risk LBCL is being investigated in the ZUMA-12 phase II clinical trial (NCT03761056). Interim study results have been previously reported by The Lymphoma Hub. Here, we summarize results from the primary analysis, published by Neelapu, et al., in Nature Medicine.1

Study design

The study is a multicenter, open-label, single-arm, phase II trial in adult patients with high-grade confirmed LBCL. High grade was defined as the presence of MYC and BCL2 and/or BCL6 translocations, or an International Prognostic Index ≥3 at any time prior to enrolment. Further information on the study design can be found here.


  • In total, 42 patients were enrolled between February 6, 2019, and October 22, 2020, of which 40 patients received an axi-cel infusion. The safety analysis included 40 patients (median follow-up, 17.4 months; range, 6.0–26.7 months), with 37 patients in the efficacy analysis (median follow-up, 15.9 months; range, 6.0–26.7 months).
  • Accrual is now complete; patients were recruited from the USA (n = 33, centers), Australia (n = 7, single center), and France (n = 2, single center).
  • Key patient baseline characteristics are summarized in Table 1.

Table 1. Key patient baseline characteristics in ZUMA-12*

Baseline characteristic, n (%)
(unless otherwise stated)

N = 40

Median age (range), years

61 (23–86)

≥65 years

15 (38)


27 (68)

Disease stage III–IV

38 (95)

ECOG Performance Status ≥1

25 (63)

One prior systemic line

32 (100)

Double- or triple-hit only

6 (15)

Double- or triple-hit and IPI ≥3

4 (10)

IPI ≥3 only

20 (50)

Deauville score



19 (48)


21 (53)

Alterations by FISH



19 (48)


15 (38)


10 (25)

Previous systemic therapy



19 (48)


18 (45)

              Neither R-CHOP nor DA-EPOCH-R

6 (15)

DA-EPOCH-R, etoposide phosphate, prednisone, vincristine sulphate (Oncovin), cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), and rituximab; ECOG, Eastern Cooperative Oncology Group; FISH, fluorescence in situ hybridization; IPI, International Prognostic Index; R-CHOP, rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine (Oncovin) and prednisone.
*Data from Neelapu, et al.1

  • Efficacy outcomes were reported in 37 patients, these included:
    • Complete response rate: 78% (95% confidence interval [CI], 62–90)
    • Objective response rate: 89% (95% CI, 75–97)
    • Median time to first complete response was 30 days (range, 27–207 days)
    • Median time to first objective response was 29 days (range, 27–207 days)
    • Partial response was 11% (n = 4)
    • Stable disease was 8% (n = 3)
  • At median follow-up of 15.9 months:
    • Objective response was 73%
    • Duration of response, event-free survival, and progression-free survival were not reached
  • With regards to safety, of 40 patients included in the analysis:
    • Overall, 34 patients experienced ‘any adverse event’ (85%)
    • The most common Grade ≥3 events are summarized in Table 2
    • No Grade 5 events occurred
  • In terms of neurological events:
    • Grade ≥3 cytokine release syndrome occurred in three patients (8%)
    • Grade ≥3 neurological events occurred in nine patients (23%)
    • No patients died from neurological events
  • In total, six patients died (18%):
    • Four patients died from progressive disease
    • Two patients died from COVID-19

Table 2. Most common Grade ≥3 adverse events in patients receiving axi-cel*

Adverse event, n (%)

N = 40


5 (13)

Reduced neutrophil count

21 (53)

Reduced white cell count

17 (43)


12 (30)


6 (15)


6 (15)


5 (12)

*Data from Neelapu, et al.1

Considering biomarkers and CAR T-cell levels:

  • CAR T-cell expansion was seen in all 40 patients
  • Median time to peak circulating CAR T-cells was 8 days (range, 8–37 days)
  • Median peak CAR T-cell level was 36.27 cells µl-1

No statistical significance was found between median peak levels of CAR T-cells in patients who relapsed/did not respond, and those who had an ongoing response to axi-cel. Several cytokines were found to be at least doubled in patients who experienced Grade ≥3 neurological events, including interleukin (IL)-5, macrophage inflammatory protein-1α (MIP-1α), interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), ferritin, tumor necrosis factor (TNF)-α, IL-10, IL-8, and programmed death-ligand 1 (PDL1) (p < 0.05).


The primary analysis of the ZUMA-12 phase II trial suggests that axi-cel has potential as a safe and effective option for the frontline treatment for high-grade LBCL. In the cohort of 37 efficacy-evaluable patients, objective response rate and complete response rate were 89% and 78%, respectively, and CAR T-cell expansion was observed in all participants. Safety data is comparable to other studies using axi-cel, with manageable adverse events and toxicities. Larger, randomized control studies are needed to replicate these results in large study populations and further compare efficacy and safety data with current standard-of-care treatment.

  1. Neelapu S, Dickinson M, Munoz J, et al.Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022. Online ahead of print. DOI: 1038/s41591-022-01731-4

Understanding your specialty helps us to deliver the most relevant and engaging content.

Please spare a moment to share yours.

Please select or type your specialty

  Thank you


Subscribe to get the best content related to lymphoma & CLL delivered to your inbox