Zevor-Cel Shows Long-Term Efficacy in Small R/R Multiple Myeloma Population

Treatment with zevorcabtagene autoleucel (zevor-cel) demonstrated long-term efficacy and manageable toxicity in a small cohort of patients with relapsed/refractory multiple myeloma, according to data from the phase 1 portion of the LUMMICAR study 1 (NCT03975907) published in Blood Advances.¹

After a median follow-up of 53.3 months (range, 14.8-63.5), data showed an objective response rate (ORR) of 100% (95% CI, 76.8%-100.0%), with 66.7% (n = 2/3; 95% CI, 9.4%-99.2%) of those receiving 100 x 10⁶ cells of zevor-cel achieving a complete response (CR) or stringent CR (sCR) compared with 81.8% (n = 9/11; 95% CI, 48.2%-97.7%) of those who received the agent at 150 x 10⁶ cells. In each respective dosing cohort, the very good partial response (VGPR) rates were 100% (n = 3/3; 95% CI, 29.2%-100.0%) and 90.9% (n = 10/11; 95% CI, 58.7%-99.8%), the median progression-free survival (PFS) was not evaluable (NE; 95% CI, 3.7-NE) and 24.7 months (95% CI, 14.9-NE), and the median PFS among those with a CR or better was NE (95% NE-NE) and 26.91 months (95% CI, 15.1-NE).

The median overall survival (OS) was NE among patients who received zevor-cel at 100 x 10⁶ cells (95% CI, 42.6-NE) as well as those received the agent at 150 x 10⁶ cells (95% CI, 32.6-NE). Data showed a median time to response of 29.0 days (range, 28-29) and 28.0 days (range, 27-29) in each respective cohort, and the median duration of response (DOR) was NE (95% CI, 2.8-NE) and 23.9 months (95% CI, 14.0-NE).

Measurable residual disease (MRD) status was evaluable in 3 patients from the 100 x 10⁶ dosing cohort and 10 of those in the 150 x 10⁶ cohort. MRD-negative status at a threshold of less than 10^–5 occurred in 66.7% (n = 2/3; 95% CI, 9.4%-99.2%) and 100.0% (n = 10; 95% CI, 69.2%-100.0%).

“At 53.3 months of median follow-up, zevor-cel demonstrates compelling antitumor activity without conferring any safety disadvantages as evidenced by the lack of higher-grade cytokine release syndrome [CRS] or neurotoxicity. However, as in phase 1 clinical trials, the limited sample size of this study may not adequately characterize the safety profile of zevor-cel,” lead study author Chengcheng Fu, MD, from the National Clinical Research Center for Hematologic Diseases at Jiangsu Institute of Hematology of The First Affiliated Hospital of Soochow University, wrote with coauthors in the publication.¹ “We aim to address these limitations by expanding the sample size, increasing the diversity and representativeness of the trial, and improving the generalizability of the data through multicenter phase 2 clinical trials of LUMMICAR study 1 and LUMMICAR study 2 (NCT03915184).”

In the ongoing, single-arm, open-label phase 1/2 study, patients were assigned to receive zevor-cel at 100 x 10⁶ (n = 3) or 150 x 10⁶ CAR T cells (n = 3) during the dose-escalation portion and 150 x 10⁶ CAR T cells in the dose-expansion stage (n = 8). Additionally, all patients underwent a lymphodepletion regimen including fludarabine at 25 mg/m² plus cyclophosphamide at 300 mg/m² at 5 to 3 days before treatment with zevor-cel.

The trial’s primary end point was the safety and tolerability of zevor-cel. Secondary end points included efficacy based on MRD negativity, time to response, ORR, DOR, PFS, and OS.²

Patients 18 to 75 years old with at least 3 prior lines of treatment for multiple myeloma, including at least 1 proteasome inhibitor and 1 immunomodulatory drug; measurable disease; and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial. Other requirements for study entry included having an estimated life expectancy of more than 12 weeks and adequate organ function.

Across the overall population, the median age was 54.0 years (range, 34-62), and 50% each were male and female. Additionally, 50.0% of patients each had an ECOG performance status of 0 or 1. Most patients had IgG immunoglobulin (42.9%), International Staging System stage II disease (50.0%), and no extramedullary disease (85.7%). The most common prior proteasome inhibitor was bortezomib (Velcade; 100.0%), and the most common type of immunomodulatory drug was lenalidomide (Revlimid; 78.6%).

Safety data revealed no dose-limiting toxicities. CRS occurred in 92.9% of patients, with all events being grade 1 or 2. Investigators reported no immune effector cell-associated neurotoxicity syndrome (ICANS), Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome.

The most common any-grade treatment-emergent adverse effects (TEAEs) included decreased lymphocyte counts (100.0%), decreased neutrophil counts (100.0%), decreased white blood cell counts (100.0%), decreased platelet counts (85.7%), and increased alpha hydroxybutyrate dehydrogenase (64.3%). Deaths occurred in 3 patients (21.4%), and there were no instances of second primary malignancy or autoimmune diseases.

References

1. Fu C, Chen W, Cai Z, et al. Long-term follow-up of zevor-cel in patients with relapsed/refractory multiple myeloma. Blood Adv. 2026;10(2):468-478. doi:10.1182/bloodadvances.2025017365
2. Clinical trial to evaluate CT053 in patients with relapsed and/​or refractory multiple myeloma (LUMMICAR STUDY 1). ClinicalTrials.gov. Updated March 12, 2024. Accessed January 19, 2026. https://tinyurl.com/kyrdvn7y