Real-World Early Outcomes With Brexu-Cel in MCL Demonstrate Feasibility and Positive Efficacy

Despite its use in a population with broad characteristics and high-risk features, a real-world outcome analysis demonstrated brexucabtagene autoleucel’s feasibility and efficacy in those with mantle cell lymphoma.

An assessment of real-world outcomes with brexucabtagene autoleucel (brexu-cel; Tecartus) in patients with mantle cell lymphoma (MCL) indicated that the CAR T-cell therapy was both feasible and efficacious, despite being used in a population with a broad range of baseline characteristics and high-risk features.1

The median time to initial response was 30 days (range, 16-104) following treatment with brexu-cel, with a 30-day overall response rate (ORR) of 88% in an evaluable population of 92 patients, including a complete response (CR) rate of 66% and a partial response (PR) rate of 22%.

Notably, best ORR in the real-world study was 89%, which was comparable to the phase 2 ZUMA-2 trial (NCT02601313), which reported a rate of 93%.2 Additionally, 9% of patients had progressive disease and 1% had stable disease. One of 2 patients with stable disease at day 30 achieved a CR after a median of 64 days.

When responses were assessed by patient subgroup, investigators reported an ORR of 95% and CR rate of 87% in those with blastoid/pleomorphic morphology (n = 39); 87% and 71%, respectively, for those with a TP53 deletion or mutation (n = 31); 90% and 78% in those with a Ki67 percentage score of 50% of more (n = 50); 82% and 64% in those with a high score by the Simplified Mantle Cell Lymphoma international Prognostic Index (n = 11); and 86% and 57% for those with central nervous system (CNS) involvement (n = 7). Additionally, patients who were Burton tyrosine kinase (BTK) inhibitor naïve (n = 17) experienced an ORR of 94% and a CR rate of 88%, and those ineligible for the ZUMA-2 trial (n = 74­) had rates of 91% and 80%, respectively.

In terms of additional study findings, investigators reported that the median duration of response (DOR) had not been reached after a median follow-up of 6.7 months (range, 0.5-13.6). The 6-month DOR rate was 70% (95% CI, 57%-80%), which was found to be comparable with findings from ZUMA-2. Additionally, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 6- and 12-month PFS rates were 66% (95% CI, 54%-75%) and 51% (95% CI, 37%-64%), respectively. Moreover, the 6- and 12-month OS rates were 81% (95% CI, 70%-88%) and 72% (95% CI, 57%-82%), respectively.

Eligibility criteria for the ZUMA-2 trial included having between 1 to 5 prior lines of therapy, including an anti-CD20 agent, anthracycline or bendamustine, and ibrutinib (Imbruvica) or acalabrutinib (Calquence); an ECOG performance status of 2 or lower; adequate blood counts, hepatic function, and renal function; and no significant comorbidities. Bridging therapies included corticosteroids, ibrutinib, and acalabrutinib.2

A total of 14 centers participated in the study, which included patients who underwent leukapheresis by June 2021 to manufacture brexu-cel. Investigators collected data relating to clinical characteristics, bridging therapy, adverse effects (AEs) following brexu-cel treatment, and outcomes following infusion.

One hundred and seven patients underwent leukapheresis, 12 of whom did not go on to receive an infusion due to manufacture failure (n = 6), organ dysfunction (n = 1), or death (n = 5). Ninety-five patients received a brexu-cel infusion.

Patients included in the analysis had a median age of 67 years (range, 34-89) and most were men (80%). Additionally, 57% of patients had a Ki-67 percentage score of 50% or more and 41% had blastoid/pleomorphic morphology (41%). Forty-four percent of patients had a TP53 mutation or deletion and 29% had a complex karyotype.

Treatment-related reasons for ZUMA-2 ineligibility included receiving over 5 lines of therapy (13%), not previously receiving a BTK inhibitor (18%), or not receiving a previous CD20 agent, anthracycline, or bendamustine (14%). Other reasons for ineligibility included having an absolute neutrophil count of less than 1000/µL (8%), an absolute lymphocyte count of less than 100/µL (1%), a platelet count of less than 75,000/µL (5%), a creatinine level of more than 1.5 mg/dL (8%), or creatinine clearance of less than 60 mL/minute (20%). Notably, 78% of patients included in the analysis would not have met inclusion criteria for the ZUMA-2 trial.

In total, 67% of patients underwent bridging therapy, with a median time from leukapheresis to lymphodepleting chemotherapy of 23 days. The median time from lymphodepleting chemotherapy to CAR T-cell infusion was 5 days.

Among those treated, 91% developed cytokine release syndrome (CRS) and 60% developed immune effector cell–associated neurotoxicity syndrome (ICANS). Eight percent of all CRS events and 35% of ICANS events were grade 3 or 4 in severity. The incidence of CRS and ICANS were comparable with events that were observed in the ZUMA-2 trial. Median time to onset of events was 4 and 6 days, respectively, and a median duration of 5 and 6 days. The events were most commonly managed with tocilizumab (Actemra; 79%), steroids (69%), which appeared to be more frequent than in ZUMA-2. Twenty-one percent of patients were admitted to intensive care for a median of 3 days, with 11% needing vasopressors, 4% needing mechanical ventilation, and 3% needing dialysis (3%).

These findings were presented at the 2022 Tandem Meeting.

References

  1. Munoz J, Wang Y, Jain P, et al. Brexucabtagene autoleucel for relapsed/refractory mantle cell lymphoma: real world experience from the US lymphoma CAR T consortium. Presented at: 2022 Transplantation & Cellular Therapy Meetings; Salt Lake City, UT; April 23-26, 2022. Abstract 265.
  2. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020;382(14):1331-1342. doi:10.1056/NEJMoa1914347