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

Introducing

Now you can personalise
your Lymphoma Hub experience!

Bookmark content to read later

Select your specific areas of interest

View content recommended for you

Find out more
  TRANSLATE

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

The Lymphoma & CLL Hub is an independent medical education platform, sponsored by Beigene and Roche, and supported through educational grants from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Lilly, Pfizer, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC View funders.

2021-04-26T09:36:17.000Z

ZUMA-1 4-year follow-up: Polyclonal B-cell recovery and survival outcomes with axi-cel in R/R large B-cell lymphoma

Apr 26, 2021
Share:

Bookmark this article

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy with a CD28 transmembrane/co-stimulatory domain, approved for the treatment of relapsed/refractory (R/R) large B-cell lymphoma after ≥2 prior therapies. Approval was based on the phase I/II ZUMA-1 (NCT02348216) trial results.

Positive results from the 2-year analysis of the ZUMA-1 trial were previously reported on the Lymphoma Hub, where 83% of patients responded, 58% achieved a complete response, and 39% had ongoing responses after a median follow-up of 27.1 months.

Here, we report the survival outcomes and recovery of polyclonal B cells for ongoing responders with 4 years of follow-up from this phase II trial, as presented by Caron Jacobson during the 47th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT).1

Patient disposition

  • A total of 111 eligible patients were enrolled in the intent-to-treat population (ITT).
  • Patients who went on to receive axi-cel treatment were categorized as the modified ITT population (MITT; n = 101).
  • Patients with ongoing responses at ≥3 years of follow-up who had evaluable samples were included in the 4-year follow-up analysis.
  • The median follow-up time was 51.1 months.

Results

Time to response (as previously reported in the 2-year follow-up), time to next anticancer therapy, and overall survival (OS) after ≥4 years of follow up are shown in Table 1

Table 1. Time to response, time to next therapy, median OS, and 4-year OS rates*

Response 

ITT population
(n = 111) 

MITT population
(n = 101)  

Median time to OR, months (range)

1.7 (0.7–12.9)

1 (1–12)

Median time to CR, months (range)

1.9 (0.7–13.3)

1 (1–12)

Median time to next therapy, months (range)

— 

8.7 (0.3–53.8)

Median OS, months

17.4

25.8

KM estimate of 4-year OS rate, %

41

44

CR, complete response; ITT, intention to treat; KM, Kaplan Meier; MITT, modified intention to treat; OR, objective response; OS, overall survival.
*Data from Jacobson et al.1
Time from axi-cel infusion to initiation of new anticancer therapy, including CAR T-cell treatment and excluding stem cell transplantation, or death from any cause.

Safety

  • Since study initiation, 59% of patients in the ITT population have died.
  • Since the 2-year data cut-off date,
    • Eight deaths occurred, due to either progressive disease (n = 5), secondary malignancy (n = 1), cardiac arrest (n = 1), or unknown cause (n = 1).
    • No new axi-cel–related serious adverse events were reported.
    • Intravenous immunoglobulin therapy was received by four patients.
  • At the 4-year data cut-off,
    • No new axi-cel–related secondary malignancies were reported.
    • There were no confirmed cases of replication-competent retrovirus.

CAR T-cell expansion and B-cell recovery

  • Ongoing responders after 2 years had greater CAR T-cell expansion in the blood after 7–14 days of axi-cel infusion compared to patients who experienced relapse (p = 0.014) or no response (p = 0.0003).
  • At 3 years after axi-cel treatment, all evaluable patients (n = 21) had detectable B cells in the blood; 67% had detectable CAR gene-marked cells and polyclonal B cells.
  • 91% of patients with ongoing response at ≥3 years of follow-up (n = 21 out of 23) demonstrated polyclonal B-cell recovery as measured by the presence of kappa and lambda light chains on non-malignant CD19+ and/or CD20+ B cells. The median immunoglobulin kappa–lambda ratio was 1.6.
  • Diversification of the B-cell population, including memory and naive B-cell immunophenotypes, indicated reconstitution of the B-cell repertoire.

Conclusion

In this long-term follow-up of the ZUMA-1 trial, axi-cel demonstrated deep and durable responses, with a 4-year OS rate of 44% among treated patients. The short time between enrolment and response, as previously observed, demonstrates the speed at which the therapy takes effect.

Moreover, patients with ongoing responses at ≥3 years of follow-up showed evidence of polyclonal B-cell restoration and clearance of functional CAR-T cells, which is a key component of the long-term safety of CD19-directed CAR T-cell therapy. This also supports the idea that persistence of functional CAR T cells is not necessary for deep and durable remission in large B-cell lymphoma.

  1. Jacobson CA, Locke FL, Ghobadi A, et al. Long-term survival and gradual recovery of B cells in patients with refractory large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel). Oral abstract #19-2. 47th Annual Meeting of the EBMT; March 14, 2021; Virtual.

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

Your opinion matters

HCPs, what is your preferred format for educational content on the Lymphoma Hub?
44 votes - 79 days left ...

Newsletter

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