Relma-cel Demonstrates Durable Activity in Relapsed/Refractory LBCL

Relmacabtagene autoleucel (relma-cel; Carteyva) elicited durable responses and a high overall survival (OS) rate in Chinese patients with relapsed/refractory large B-cell lymphoma (LBCL), according to 2-year follow-up data from the phase 2 RELIANCE trial (NCT04089215) presented during the 2022 ASCO Annual Meeting.¹

At a median follow-up of 24 months (95% CI, 23.9-24.1) , the best overall response rate (ORR) achieved with the autologous CD19-targeted CAR T-cell therapy was 77.6% among 58 evaluable patients, which included a complete response (CR) rate of 53.5%. The median duration of response (DOR) was 20.3 months (95% CI, 4.86–not estimable [NE]), and the 2-year DOR rate was 40.3%.

Moreover, the median progression-free survival (PFS) with the therapy was 7 months (95% CI, 4.76-24.15), and the median OS was not yet reached. The 2-year PFS and OS rates were 38.8% and 69.3%, respectively.

“Relma-cel demonstrated durable responses with a high 2-year overall survival [OS] rate,” lead study author Zhitao Yang, MD, of the Department of Lymphoma and Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) of Peking University Cancer Hospital & Institute in Beijing, China, and colleagues, wrote in a poster presentation of the data. “The median OS has not yet been reached for responding patients, and [there was] a manageable safety profile.”

RELIANCE was the first study of a CD19-directed CAR T-cell therapy to receive investigational new drug approval by the China National Medical Products Administration. Prior results from the study showed high response rates and low toxicity with relma-cel.

The study enrolled patients who were 18 years or older with histologically LBCL who received at least 2 prior lines of therapy. Patients were required to have an ECOG performance status of 0 or 1, an accessible PET-positive lesion, a measurable CT-positive lesion, adequate organ function, and acceptable vascular access for leukapheresis.² Those who received prior CD19-targeted therapy needed to confirm that their lesions still expressed CD19.

Key exclusion criteria included central nervous system (CNS)–only involvement, a history of another primary malignancy that has not been in remission for at least 2 years, or any history of a serious cardiovascular disease, among others.

Fifty-nine adult patients were randomized to receive relma-cel at 100 x 10⁶ CAR-positive T cells or 150 x 10⁶ CAR-positive T cells. Prior to CAR T-cell infusion, all patients received lymphodepleting chemotherapy, and some received bridging chemotherapy.

The primary end point of the study was 3-month ORR. Secondary end points included 3-month CR rate, DOR, PFS, OS, and safety.

Additional data showed that among evaluable patients who received relma-cel at 100 x 10⁶ CAR-positive T cells (n = 21), the median DOR was 23.3 months (95% CI, 5.16-NE). Those who were administered the therapy at 150 x 10⁶ CAR-positive T cells (n = 24), experienced a median DOR of 6.0 months (95% CI, 2.99-NE).

In patients who received relma-cel at 100 x 10⁶ CAR-positive T cells (n = 27), the median PFS was 8.8 months (95% CI, 5.55-NE). For those who received the therapy at 150 x 10⁶ CAR-positive T cells (n = 31), the median PFS was 5.5 months (95% CI, 2.96-21.19).

Regarding safety, 91.5% of patients experienced at least 1 treatment-related adverse effect (TRAE) with relma-cel, and 55.9% had at least 1 effect that was grade 3 or higher in severity. Any-grade cytokine release syndrome (CRS) and neurotoxicity occurred in 47.5% and 20.3% of patients, respectively; these effects were grade 3 or higher in 5.1% and 3.4% of patients, respectively.

The median duration of any-grade CRS was 7 days (range, 1-118), and the median time to CRS was 4 days (range, 1-10). The median duration of any-grade neurotoxicity was 12.5 days (range, 1-49), and the median duration of neurotoxicity was 8.5 days (range, 2-11).

The other most common grade 3 or higher TRAEs included neutropenia (40.7%), leukopenia (22%), lymphopenia (11.9%), thrombocytopenia (11.9%).

Although relma-cel has shown to have manageable safety and to produce substantial durable responses in this population, further follow up is needed, according to the study authors.

References

1. Ying Z, Song Y, Yang H, et al. Two-year follow-up result of RELIANCE study, a multicenter phase 2 trial of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma. J Clin Oncol. 2022;40(suppl 16):7529. doi:10.1200/JCO.2022.40.16_suppl.7529
2. CD19-targeted CAR T cells for relapsed and refractory (R/R) non-Hodgkins lymphoma. ClinicalTrials.gov. Updated January 22, 2021. Accessed August 17, 2022. https://clinicaltrials.gov/ct2/show/NCT04089215