FDA Approves Label Updates to Include New Data for Axi-Cel in LBCL, Zanubrutinib in CLL


The FDA has approved label updates for zanubrutinib to include data from the ALPINE trial in relapsed/refractory chronic lymphocytic leukemia, and axicabtagene ciloleucel to include findings from the primary overall survival analysis of the ZUMA-7 trial in relapsed/refractory large B-cell lymphoma.

The FDA has approved label updates for zanubrutinib (Brukinsa) to include positive progression-free survival (PFS) data from the phase 3 ALPINE trial (NCT03734016) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), and axicabtagene ciloleucel (axi-cel; Yescarta) to include findings from the primary overall survival (OS) analysis of the phase 3 ZUMA-7 trial (NCT03391466) in patients with relapsed/refractory large B-cell lymphoma (LBCL).1,2

The updated label for zanubrutinib is based on data from a prespecified analysis of the ALPINE trial that was presented at the 2022 ASH Annual Meeting and Exposition in which the second-generation BTK inhibitor led to an improvement in PFS vs ibrutinib (Imbruvica) and showcased a favorable cardiac safety profile in patients with relapsed/refractory CLL. At a median follow-up of 31 months, zanubrutinib demonstrated a 35% reduction in the risk of progression or death vs ibrutinib according to both investigator and independent committee review assessment (HR, 0.65; 95% CI, 0.49-0.86; P = .0024).In terms of safety, zanubrutinib led to lower rates of atrial fibrillation/flutter (5.2% vs 13.3% for zanubrutinib and ibrutinib, respectively) and deaths due to cardiac disorders (0% vs 1.9%).1

“The ALPINE trial is the first and only study to demonstrate PFS superiority in a head-to-head comparison versus ibrutinib in CLL,” Mehrdad Mobasher, MD, MPH, chief medical officer of Hematology at BeiGene, stated. “[Zanubrutinib] was approved in the US for CLL at the beginning of 2023, and we submitted additional data from the ALPINE PFS analysis supporting it as the BTK inhibitor of choice in CLL, solidifying it as an important treatment option for patients. When making treatment decisions, it is critical that physicians and patients understand the totality of data supporting [zanubrutinib]’s robust efficacy and differentiated safety in CLL.”

The label update for axi-cel is based on findings from the ZUMA-7 trial in which treatment with the CD19-directed CAR T-cell therapy led to a 27.4% reduction in the risk of death vs standard of care (SOC) as second-line therapy with curative intent in patients with relapsed/refractory LBCL within 12 months of completing first-line therapy. At median follow-up of 46.7 months, the estimated 39-month OS rates were 55.9% and 46% with axi-cel and SOC, respectively.2

“This US label update for [axi-cel] is an important step to reinforce health care provider confidence to treat eligible patients with [axi-cel], immediately following progression or relapse in large B-cell lymphoma,” Frank Neumann, MD, PhD, senior vice president and global head of Clinical Development at Kite, stated in a news release.1 “Our ZUMA-7 OS analysis proves that when given as second-line therapy, [axi-cel] is even more effective in improving patient survival than standard of care treatment. Coupled with our rapid and reliable manufacturing, it is our hope to provide patients a chance to live longer lives.”

In the randomized, global phase 3 ALPINE trial, 652 patients with relapsed/refractory CLL or small lymphocytic lymphoma were randomly assigned to receive 160 mg of zanubrutinib twice daily or 420 mg of ibrutinib daily until disease progression or unacceptable toxicity.3

Objective response rate (ORR) served as the primary end point of the study, with key secondary end points of PFS, duration of response, time to treatment failure, OS, patient-reported outcomes, and safety.3

Updated results from the ALPINE trial, which recently presented at the 2023 ASH Annual Meeting and Exposition with a median follow-up of 39 months, showed that zanubrutinib led to sustained improvement in PFS vs ibrutinib (HR, 0.68; 95% CI, 0.53-0.86; P=.0011). Zanubrutinib also demonstrated durable PFS improvement across subgroups, including patients with 17p deletion or TP53 mutation (HR, 0.52; 95% CI, 0.33-0.83; P=.0047).1,3

Safety findings from the updated analysis proved consistent with prior results. The most frequent treatment-emergent adverse effects that occurred in at least 20% of patients who received zanubrutinib were COVID-19-related, neutropenia, hypertension, and upper respiratory tract infection.

In the randomized, open-label, global, multicenter, phase 3 ZUMA-7 trial 359 patients with relapsed/refractory LBCL within 12 months of frontline therapy were randomly assigned to receive one infusion of axi-cel or SOC therapy. The primary end point was event-free survival (EFS) evaluated by blinded central review. Key secondary end points included ORR, OS, patient reported outcomes, and safety.2

Prior results showed that axi-cel led to a 2-year EFS rate of 40.5% vs 16.3% with SOC. The median EFS was 8.3 months and 2.0 months with axi-cel and SOC, respectively (HR, 0.398; 95% CI, 0.308-0.514; P<.0001). Additionally, 94% of patients assigned to treatment with axi-cel received the therapy vs 35% of those assigned to SOC. Regarding response, the ORR was higher with axi-cel, at 83% vs 50% with SOC (odds ratio: 5.31; 95% CI, 3.1-8.9; P<.0001). More complete responses were also achieved with axi-cel vs SOC, at 65% vs 32%, respectively.

Regarding safety with axi-cel (n = 168), grade 3 or greater cytokine release syndrome and neurologic events occurred in 7% and 25% of patients, respectively. In the SOC arm, 83% of patients had high-grade events, most of which were cytopenias.


  1. FDA approves label update for BRUKINSA (zanubrutinib) in chronic lymphocytic leukemia (CLL). News release. BeiGene. December 22, 2023. Accessed December 22, 2023. https://ir.beigene.com/news/fda-approves-label-update-for-brukinsa-zanubrutinib-in-chronic-lymphocytic-leukemia-cll/49b1ba2a-1f61-4034-9371-292f81d2ca57/
  2. U.S. FDA approves label update for Kite’s Yescarta CAR T-cell therapy to include overall survival data. News release. Kite. December 21, 2023. Accessed December 22, 2023. https://investors.gilead.com/news/news-details/2023/U.S.-FDA-Approves-Label-Update-for-Kites-Yescarta-CAR-T-Cell-Therapy-to-Include-Overall-Survival-Data/default.aspx
  3. Brown JR, Eichhorst BF, Lamanna N, et al. Extended follow-up of ALPINE randomized phase 3 study confirms sustained superior progression-free survival of zanubrutinib versus ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL). Blood. 2023;142(1):202. doi:10.1182/blood-2023-174289
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