Real-World Efficacy and Safety of Teclistamab for Patients with Released or Refractory Multiple Myeloma: Korean, Nationwide, Retrospective Analysis of an Named Patient Program
Authors: Yi Jun Ho , Lee Jae Hoon , Jung Sung-Hoon , Lee Ji Hyun , Lee Ji Yun , Kim Kihyun , Park Sung-Soo , Min Chang-Ki , Choi Yoon Seok , Kim Min Kyoung , Yhim Ho-Young , Yoon Dok Hyun 
Published: December 2024

Introduction
The outcomes of heavily treated relapsed or refractory multiple myeloma (RRMM) are dismal. Teclistamab (Tec) is a bispecific BCMA-CD3 directed T-cell antibody (BsAb) which was approved in triple-class exposed RRMM patients who have received at least three prior lines of therapy. Its efficacy has been demonstrated in the MajesTEC-1 trial and subsequent real-world reports. However, consistent with the safety profile of BCMA BsAbs, the drug may also induce significant adverse events including infection and/or cytokine release syndrome (CRS). In addition, only a small number of Asian patients were included in the MajesTEC-1 trial, and to date, there has not been a real-world report for Asian population. To further inform the efficacy and safety of Tec in Asians, we carried out a nationwide retrospective analysis of the Tec Named Patient Program (NPP) in Korea.
Patients and Methods
From August 2022, an NPP for Tec was started in Korea. The program's inclusion and exclusion criteria, dosage, treatment schedules, and modifications closely mirrored those of the MajesTEC-1 trial. Of the 50 patients who have participated the program, retrospective data collection was done in 42 patients.
Results
From October 2022 to March 2023, 42 consecutive patients (M:F=27:15) were included in the analysis from 10 tertiary institutes in Korea. At the time of diagnosis, the median age was 60 (range, 43-80), and 15 patients were classified as R-ISS III. Of the 39 patients whose cytogenetic data were available, 17 patients had at least one high-risk factor by FISH. Patients had received a median of 6 (range, 3-10) lines of prior therapy, 21 patients (50.0%) had received autologous stem cell transplantation. Seventeen patients (40.5%) were triple-class refractory, and three had been exposed to belantamab mafodotin.
Patients received Tec at the median age of 67 (range, 48 - 84), and 39 patients (92.8%) were in ECOG PS 0-2 (ECOG 0-14; 1-19; 2-6). Twelve patients had extramedullary disease. The overall response and the CR rate was 66.7% and 40.5%, respectively (sCR/CR 17; VGPR 5; PR 6; SD 1; PD 13), and the median time to response was 1.6 months (95% CI, 0.9-2.3). With a median follow-up duration of 16.4 months (95% CI, 15.1 - 17.7), the median PFS was 14.1 months, and the median DoR was not reached. The 12-month DoR rate was 55.0%, and 70.3% for patients who achieved CR;, this was significantly higher than for non-CR patients (36.7%, p = 0.045). The median OS was not reached, and the 12-month OS rate was 61.7% (95% CI, 53.8-69.6%). The most common cause of death was progressive disease (n=16) followed by infection (n=7). Baseline R-ISS III was associated with significantly shortened PFS (p = 0.041).
Twenty patients (47.6%) experienced CRS, and there were 27 CRS events with only 1 event was grade 3 CRS. Thirteen CRS events occurred during SUD period, and after the completion of cycle 1, only 1 CRS event occurred which was resolved with the use of steroid. No ICANS occurred. The most common grade 3~4 hematologic adverse events (AEs) were neutropenia (n=27, 64.3%), but only 2 patients experienced febrile neutropenia. Other hematologic AEs included thrombocytopenia (n=21, 50.0%), leukopenia (n=19, 45.2%), and anemia (n=14, 33.3%). In terms of grade 3~4 non-hematologic AEs, 18 patients (42.9%) experienced infection, including 9 events of COVID-19 infection.
Twenty-seven patients (64.3%) had treatment holds for infection (n=18), and hematologic AEs (n=8). Three patients experienced dose reduction for general deterioration.
CONCLUSION
This is one of the few reports that included a relatively large number of Asians with an extended follow-up duration. Efficacy, including a rapid response, a high ORR, and prolonged PFS and OS, and safety profiles including rates of infectious events, CRS, and ICANS were comparable to those of the MajesTEC-1 trial. The use and impact of IVIg, prophylactic antibacterial/antifungal agents will be presented in the meeting.