Outcomes of patients aged ≥26 years with relapsed or refractory B-cell acute lymphoblastic leukemia in ZUMA-3 and historical trials

Monique C. Minnema, Xiang Yin, Ruthanna Davi, Sam Keeping, Julie E. Park, Taha Itani, Tsveta Hadjivassileva, Jean-Gabriel Castaigne, Rita Damico Khalid, Lang Zhou, James J. Wu & Bijal D. Shah (24 May 2024): Outcomes of patients aged ≥26 years with relapsed or refractory B-cell acute lymphoblastic leukemia in ZUMA-3 and historical trials, Leukemia & Lymphoma, DOI: 10.1080/10428194.2024.2353877

Brexu-cel is the first and only CAR T-cell therapy currently approved for the treatment of patients aged ≥26 years with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) in the EU.1 Additionally, it is approved for the treatment of patients aged ≥18 years with R/R B-ALL in Israel.2
In the ZUMA-3 Phase 2 trial, brexu-cel demonstrated a significant benefit with a complete response/complete response with incomplete hematologic recovery (CR/CRi) rate of 72%, median relapse-free survival (RFS) of 10.3 months, and median overall survival (OS) of 25.4 months in patients aged ≥26 years. This efficacy is consistent with the results previously published for ZUMA-3 Phase 2 patients aged ≥18 years.3 Additionally, there was no significant difference in safety between this population and the overall ZUMA-3 Phase 2 population.3
Given that ZUMA-3 is a single-arm study, two different methods, SCHOLAR-34 and a matching-adjusted indirect comparison (MAIC) study5, were employed to evaluate the benefit of ZUMA-3 relative to SOC therapies in patients with R/R B-ALL.
These two comparative analyses indicate that brexu-cel had better outcomes and a lower risk of death compared to standard of care (SOC) therapies, including blinatumomab and inotuzumab ozogamicin, with a 56% reduction in the risk of death versus inotuzumab ozogamicin, a 52% reduction versus blinatumomab, and a 66% reduction versus chemotherapy.

In summary, this analysis showed that patients aged ≥26 years in the ZUMA-3 trial benefited from brexu-cel with efficacy and safety comparable to the overall patient population. Additionally, the advantage of brexu-cel over SOC therapy was significant in patients aged ≥26 years, as demonstrated through two complementary analytical approaches used to compare ZUMA-3 outcomes with other studies.

At the latest ASCO (2024) conference, the 4-year survival outcomes for ZUMA-3 were presented. With a median follow-up of 53.6 months, the data revealed a 48-month OS rate of 40%

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Full article: Outcomes of patients aged ≥26 years with relapsed or refractory B-cell acute lymphoblastic leukemia in ZUMA-3 and historical trials (tandfonline.com)
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References:

  1. TECARTUS®. (brexucabtagene autoleucel) [summary of product characteristics]. Amsterdam, The Netherlands: Kite Pharma EU B.V.; 2023.
  2. TECARTUS®. (brexucabtagene autoleucel) [prescribing information].Israel: Kite Pharma, Inc; 2023.
  3. Shah BD, Ghobadi A, Oluwole OO, et al. Two-year follow-up of KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) in ZUMA-3. J Clin Oncol. 2022;40(16):7010–7010. doi:10.1200/ JCO.2022.40.16_suppl.7010
  4. Shah BD, Ghobadi A, Oluwole OO, et al. Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. J Hematol Oncol. 2022;15(1):170. doi:10.1186/s13045-022-01379-0
  5. Shah B, Chen JMH, Wu JJ, et al. Matching-adjusted indirect comparisons of brexucabtagene autoleucel with alternative standard therapies for relapsed/refractory B-cell acute lymphoblastic leukemia in adult patients. Adv Ther. 2023;40(12):5383–5398. doi:10.1007/s12325- 023-02662-3

Tecartus

Tecartus is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after two or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor unless ineligible to BTK inhibitor.

Limitation of use: Tecartus is not indicated for the treatment of patients with active central nervous system lymphoma.

Tecartus is indicated for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).

For further information and full list of adverse events, please refer to the approved prescribing information as available at Israeli Ministry of Health website:
https://israeldrugs.health.gov.il/#!/byDrug

Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form at https://sideeffects.health.gov.il/

Additionally, adverse events can be reported to Gilead: Safety_FC@gilead.com

This article is intended for healthcare providers only.

For any further questions please contact: medinfo.israel@gilead.com

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IL-TEC-0211, June 2024