According to data presented at IMS 2023, a real-world analysis showed that teclistamab demonstrated comparable efficacy to the results observed in the phase 2 MajesTec-1 trial for patients with relapsed/refractory multiple myeloma.
Findings from a real-world study of patients with relapsed/refractory multiple myeloma showed that teclistamab (Tecvayli) had comparable efficacy with that observed in the phase 2 Majes-TEC-1 trial (NCT03145181; NCT04557098), according to a presentation given during the 2023 International Myeloma Society Annual Meeting.1
The median progression-free survival (PFS) was 4.7 months, with a median follow-up of 69.5 days. For patients who had received prior B-cell maturation antigen (BCMA) therapy, the median PFS was 4.0 months compared with those who did not which was 4.8 months (P = .48).
“Our single-center retrospective experience of teclistamab in [relapsed/refractory multiple myeloma] demonstrates similar efficacy and toxicity to the pivotal phase 2 MajesTEC-1 trial, despite 80% of our patients considered ineligible for trial inclusion,” lead study author Shonali Midha, MD, a medical oncologist from Dana-Farber Cancer Institution, said in a presentation during the meeting.
The trial's main goal was to evaluate teclistamab as a standard of care in the aforementioned patient population. To be included in the trial, patients must have the indicated disease and be treated with teclistamab by August 15, 2023. Additionally, if patients completed step-up dosing they were considered evaluable for response. If patients died prior to the 30-day response from infection, teclistamab toxicity, or disease progression, they were included in the safety and survival analysis.
Responses were graded via the International Myeloma Working Group response criteria. Regarding adverse effects of cytokine release syndrome (CRS) and neurotoxicity, the American Society of Transplant and Cellular Therapy was managed by each institution.
In the MajesTEC-1 trial, 165 patients were given teclistamab, the median follow-up was 14.1 months with an overall response rate of 63.0% and a complete response of 39.4%.2 There was no minimal residual disease in 26.7% of patients, and the MRD-negativity rate of those with a complete response or better was 46%. Additionally, the median duration of PFS was 11.3 months (95% CI, 8.8-17.1).
Results from this trial helped lead to the approval of teclistamab in October 2022.3 The approval was the first for a BCMA-directed T-cell engager.
A total of 56 patients who received standard teclistamab were evaluated, with a median age of 69 years (range, 45-83). Most patients were male (62.5%), and 50% had an ECOG performance status of 1. The presentation noted that of the patients enrolled in this study, 45 (80%) would not have been eligible for treatment on the MajesTEC-1 trial. Additionally, the median number of prior lines of therapy was 6 (4-12).
High-risk cytogenetics were analyzed, with 26.8% of patients having 17p deletion, 16.1% having t(4,14), 7.1% having t(14,16), and 39.3% having +1q21. Extramedullary disease was noted in 42.9% of patients, as well as central nervous system disease in 12.5%.
The overall response rate was 53.6%. If patients did not have prior BCMA treatment (n = 36), the response rate was 58.3%, for those with prior BCMA (n = 20) it was 45%, those who received chimeric antigen T-cell BCMA-directed therapy (n = 13) was 30.8%, prior BCMA antibody-drug conjugate therapy (n = 13) had a response of 53.8%, and extramedullary disease (n = 24) was 37.5%. Those with high-risk cytogenetics also achieved fewer responses than those who did not have them.
Regarding safety, any-grade CRS occurred in 51.8% of patients treated with teclistamab, with grade 3 or higher CRS occurring in 1.8%. The median time to onset of CRS was 5 days (range, 1-7), and the median duration of the AE was 2. Any-grade neurotoxicity occurred in 1.8% of patients. To manage these AEs, tocilizumab (Actemra) was used in 25% of patients with a median dose of 1, and 12.5% used dexamethasone.
Infectious complications occurred in 57.1% of patients. A total of 48.4% of patients experienced grade 3/4 infectious complications; however, no deaths occurred. Infections complications included upper respiratory infection (37%), pneumonia (19%), gastrointestinal issues (13%), skin and soft tissue (13%), and viremia, bacteremia, and genitourinary issues (6% each). The median onset of these AEs was 31.5 days; COVID-19 comprised 45.5% of upper respiratory infections.
“Infectious complications remain a significant concern, nearly half requiring hospitalization and inpatient management," Midha concluded.