ZUMA studies boost therapeutic potential of brexu-cel in R/R MCL

In the primary analysis of the expanded-access ZUMA-18 trial, the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel (brexu-cel) demonstrated a high level of efficacy in patients with relapsed/refractory mantle cell lymphoma (R/R MCL).

“Objective response rate (ORR) was 87 percent and median overall survival (OS) was not reached, with close to 3 years of follow-up in a heavily pretreated population,” said Dr Andre Goy from John Theurer Cancer Center, Hackensack, New Jersey, US, at ASH 2023.

ZUMA-18 included 23 patients (n=21 and 2 for cohorts* 1 and 2, respectively; median age 69 years). Prior to receiving brexu-cel, participants received optional bridging therapy** (BT) followed by lymphodepleting chemotherapy***. Cohort 1 patients also underwent leukapheresis before optional BT. Brexu-cel was given as a single IV infusion of 2×10⁶ cells/kg on day 0 (or a fixed dose of 2x10⁸ cells for patients weighing ≥100 kg). The most common prior Bruton tyrosine kinase inhibitor (BTK) used was ibrutinib (70 percent). [ASH 2023, abstract 106]

All but three patients had an ORR. Of these, 13 were complete responses (CRs; 57 percent) while seven were partial responses (PRs; 30 percent). “Both cohort 2 patients had a CR … Half of the 20 patients with response were still in ongoing response,” noted Goy.

Median duration of response was 15.1 months in responders and 20.0 months for those with CR.

Median progression-free survival was 16.1 months in all treated patients and 21.0 months in patients with CR.

At 24 months, OS rate was 58 percent. At data cutoff, 14 patients were still alive.

All 23 patients experienced any brexu-cel-related adverse event (AE). Of these, 18 were categorized as worst grade ≥3 AEs. Of the five grade 5 AEs reported, one was considered related to brexu-cel therapy (multiple organ dysfunction syndrome). Only one patient had grade ≥3 cytokine release syndrome. There were no new safety signals detected.

Median peak and area under the curve CAR T-cell levels in responders align with those seen in ZUMA-2. Goy added that there was substantial expansion in relapsed and nonresponding patients, but the numbers were too small to come up with a conclusion regarding this outcome.

Findings consistent with ZUMA-2

In ZUMA-2, median OS for patients with CR was 58.7 months. After nearly 4 years of median follow-up, 30 of the 68 enrolled patients were still alive (27 with CR).

“With 4 years of median follow-up, patients continued to benefit from brexu-cel, with a median OS of almost 5 years in patients with CR, which is remarkable in the context of R/R MCL patients who had received chemo-immunotherapy and BTK inhibition in ZUMA-2,” Goy said.

Promising for aggressive blood cancers

“Together, the results of these two studies provide strong support for continued use of brexu-cel as standard of care in the R/R MCL setting,” Goy concluded.

“The clinical results and real-world evidence … clearly support the potential for long-term response and safety of brexu-cel in aggressive blood cancers for which patients have limited treatment options,” said Dr Frank Neumann, Senior Vice President, Global Head of Clinical Development, Kite, in a press release. [https://www.gilead.com/news-and-press/press-room/press-releases/2023/12/new-analyses-presented-at-ash-2023-support-the-potential-long-term-response-and-safety-of-kites-tecartus-in-patients-with-aggressive-blood-cancers, accessed December 31, 2023]

“We are particularly encouraged that the real-world evidence demonstrates consistent outcomes for brexu-cel among a broader range of patients,” Neumann added.