CONCLUSIONS
BCMA-directed CAR T-cell therapy is only available at certain academic centers in the Midwest and requires several weeks for manufacturing, leading to a bottleneck of patients who need therapy for relapsed/refractory multiple myeloma (R/R MM). Teclistamab is an off-the-shelf BCMA-directed bispecific T-cell engager (BiTE) that could help alleviate this bottleneck. The MajesTEC-1 trial was a phase I/II study of teclistamab in patients with R/R MM. Even in patients with triple class-exposed disease, teclistamab showed deep and durable responses. However, clinical trials generally enroll fitter patients, especially when compared to the typical MM patient at the late stages of their disease. We sought to describe the real-world treatment outcomes of patients with R/R MM who received teclistamab at Indiana University (IU).
This study was conducted retrospectively at a single center. Patients who received teclistamab between October 25 th, 2022, and July 1 st, 2023, were included. Patients were hospitalized during step-up dosing. The teclistamab dosing and schedule were per standard of care. Response was assessed after each cycle based on the IMWG Uniform Response Criteria. CRS and ICANS were graded per Lee 2020, while other side effects were evaluated using CTCAE 5.0. Demographic information, response, and adverse events were reported descriptively, and survival outcomes were estimated using Kaplan-Meier analysis with Prism GraphPad 10.0.
The baseline clinical characteristics are summarized in Table 1. Compared to MajesTEC-1, patients treated in this study were older and more heavily pretreated with a higher baseline burden of disease. Many exhibited organ dysfunction and poor performance status, and 20 of 33 patients were previously exposed to BCMA-directed therapy (BDT). The median follow-up duration was 17.6 weeks. The overall response rate (ORR) was 45.5%, including one-third of patients who achieved a very good partial response (VGPR) or better. When stratified by prior exposure to BDT, ORR was 35% in previously exposed patients and was 61.5% in naïve patients. Thirteen patients died during follow-up (9 from disease progression, 3 from infection, and 1 unexplained sudden cardiac death). Median overall survival in the entire cohort was 17.7 weeks. As shown in the Kaplan-Meier analysis in Figure 2, the median OS was not reached for patients who achieved a response, while patients who did not respond had a median OS of 16.7 weeks (p=.05). CRS was observed in 12 patients (36%), with one grade 3 event requiring tocilizumab, dexamethasone, and ICU transfer for hypoxemic respiratory failure - this patient ultimately died from a hospital-acquired infection. ICANS was observed in 5 patients (15.2%), with one grade 3 event - this patient became unresponsive, requiring intubation and mechanical ventilation. Sixteen of 33 patients had an infectious complication (48.5%), while 3 patients died of a treatment-related infection (Pseudomonas pneumonia, hospital-acquired pneumonia, and sepsis from a urinary source). Grade 3 or 4 neutropenia occurred in 12.1%.
In a real-world cohort of heavily pretreated myeloma patients, including those with poor organ function, poor performance status, and prior exposure to BCMA-directed therapy, overall response to teclistamab was lower than previously observed in the MajesTEC-1 study. Achieving a PR or better led to a significantly improved OS, while survival among non-responders was poor. Receipt of prior BCMA-directed therapy led to a lower response rate. The incidence of CRS in the current study was lower than that seen in MajesTEC-1, while the rate of neurotoxicity was similar. High grade CRS and ICANS were infrequent but led to poor patient outcomes in our cohort. Despite a low rate of grade 3 or 4 neutropenia, there was a high rate of infection, even with use of prophylactic IVIG for hypogammaglobulinemia. There were 3 infection-related fatalities. This highlights the severely immunocompromised state of the patient population and the need for early recognition and improved strategies for infection prevention. The early use of BCMA BiTEs may improve access and tolerability. However, there is still a need for better understanding of resistance mechanisms.
Disclosures
Abonour:BMS, Janssen, Pfizer: Honoraria; BMS, Janssen, Takeda: Consultancy. Suvannasankha:Regeneron: Research Funding; Glaxo Smith Kline: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Meyer Squibb: Consultancy, Research Funding; Genentech: Research Funding.
