Clinical Professor of Medicine Department of Hematology, University of California at San Francisco, San Francisco, CA, USA San Francisco, United States
Introduction: Teclistamab (TEC) is a bispecific BCMA-CD3 directed T-cell antibody (BsAb), which received EMA approval on 8/24/22 and subsequent FDA approval on 10/25/22, based on the MajesTEC-1 study showing high single agent response rates (≥PR in 63.0%) in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM). Also reported were unique side effects including, cytokine release syndrome (CRS) and neurotoxicity (ICANS), and prompting the FDA/EMA to recommend inpatient monitoring during the initial step-up and first full-dose of TEC. In addition, a high incidence of infections (76.4%; ≥grade 3: 44.8%) have been reported. Thus, the IMF Immunotherapy subgroup embarked on this international analysis of real-word use of Teclistamab in RRMM.
Methods: Patients treated with Teclistamab at 6 academic centers from 3 countries (US, Greece, Spain), were included. Data was collected up until May 23, 2023.
Results: 77 patients were included in this analysis; median age was 69 (range 38-91y); 16 pts. (21%) were 75 yrs; 53% male, 68% Caucasian, 15% Hispanic, and 14% Asian. Pts received a median of 6 PLT (range 1-21); 75% were triple-class-refractory (n=44/59), 23% had high-risk cyto/fish and 32% had 1q21 gain. At least 59% of pts would not have been eligible for MajesTEC-1 (51% prior BCMA (n=26 BCMA-CAR, n=8 BCMA-ADC; n=2 BCMA-bisp; n=3 Car+ADC); 13% had CrCl < 30ml/min with 2 on HD). Median number of hospital days was 7 but 26 patients were treated entirely as outpatients (Mayo clinic Rochester and Arizona).
CRS was seen in 52% (all grade 1: except 1Gr2, 1Gr4); it generally resolved within 24 hours and was managed with either 1 dose of tocilizumab or 1-4 doses of dex. CRS was more common in patients treated in the inpatient versus outpatient (CRS 64% vs. 35%) setting. CrCl < 30 mls, did not appear to alter the incidence or severity of CRS (55%; all Gr1). ICANS was infrequent (n=5; 7%, 1 pt with Gr 4-Sz requiring HD-steroids and treatment discontinuation). Infections were common, seen in 37% of patients, and the majority of infections were reported as viral URI or CMV reactivation. No CMV organ disease and no Covid deaths occurred. The overall response rate for evaluable patients (n=56) was 61%; (sCR/CR 7; VGPR 19; PR 8; SD 11; PD 11). In pts treated with prior BCMA (n=32) the ORR was 59% (sCR 1; VGPR 14; PR 4; SD 6; PD 7). The most common reason for treatment discontinuation was PD (12%).
Conclusions: In this Real-World evaluation of Teclistamab, a high ORR was seen 61%, similar to the results of the MajesTEC-1 study. Responses were rapid and are expected to deepen over time (median f/u only 3m). CRS rates were similar to MajesTEC-1 and no unexpected toxicity was noted. Infection rates were low but may increase with longer follow-up. Details regarding the timing and types of infection and the global use of IVIG will be presented. Additional patient data will be presented at the IMS meeting from global IMWG centers.
