Bispecific T-cell engagers (BiTE) significantly prolong survival in multiple myeloma patients: study

A Korean study has shown that bispecific T-cell engagers (BiTE), a new treatment for multiple myeloma, significantly prolongs survival compared to standard of care (SOC).

The study, published in the February issue of Transplantation and Cellular Therapy, the journal of the American Society for Cellular Therapy, was conducted by a multicenter research team from institutions including the Catholic University of Korea Seoul St. Mary's Hospital and Seoul National University Hospital. It evaluated the efficacy and safety of BiTE by analyzing real-world clinical data from patients with relapsed or refractory multiple myeloma (RRMM).

The researchers analyzed registry data from 474 RRMM patients who received three or more lines of treatment between January 2021 and October 2023. They compared the BiTE treatment group (n=71) to the SOC treatment group (n=71) using propensity score matching.

The results showed that the BiTE arm significantly prolonged progression-free survival (PFS) compared to the SOC arm (median 19.2 months vs. 5.4 months, HR=0.50, 95 percent CI 0.33-0.78, p<0.01). However, no difference in overall survival (OS) was observed between the two arms.

In the BiTE arm, 52 percent (37 patients) experienced cytokine release syndrome (CRS), with the majority (41 percent) classified as grade 1 mild. Neurotoxicity was reported in 4 (5.6 percent) patients and was generally considered manageable. However, the incidence of infection was significantly higher in the BiTE arm compared to the SOC arm (81 percent vs. 49 percent, p<0.01).

There were two main types of BiTE therapies used in the study: 29 (40.8 percent) of the 71 patients in the total BiTE cohort received BiTE targeting B-cell maturation antigen (BCMA), and another 29 (40.8 percent) received BiTE that acted on a target other than BCMA. The remaining 13 (18.3 percent) were treated with a combination of BCMA-targeting and non-BCMA-targeting BiTEs.

BCMA-targeted BiTEs included elranatamab (Elrexfio), linvoseltamab, and teclistamab (Tecvayli) as monotherapy (16 patients, 22.5 percent), with some patients (13 patients, 18.3 percent) receiving a combination of these agents with a daratumumab (Darzalex)-based regimen.

Non-BCMA-targeted BiTEs included drugs such as astalquetamab (brand name Talbay), which targets GPRC5D. These treatments were used as monotherapy (17 patients, 23.9 percent) or in combination with daratumumab (12 patients, 16.9 percent).

The researchers concluded that, in a real-world clinical setting, BiTE therapy significantly improved PFS in patients with relapsed or refractory multiple myeloma compared to standard of care. They also emphasized that the observed adverse events were generally manageable and that BiTE therapy may be a promising treatment option for patients with heavily pretreated multiple myeloma.

Notably, the researchers noted that BiTEs that did not target BCMA had better clinical outcomes than BCMA-targeted BiTEs and suggested that these targeting differences warrant further investigation in larger clinical trials.

“Multiple myeloma is a blood cancer that is not only increasing in the number of patients in Korea due to the aging population but is also feared by patients due to its frequent relapses,” said Professor Min Chang-ki of the Department of Hematology at Seoul St. Mary's Hospital, co-corresponding author of the study. “Through this study, which demonstrates the effectiveness of dual antibody therapy, we plan to continue further research to provide new hope to many patients who have been unable to benefit from other treatment methods.”