Linvoseltamab Generates Efficacy Similar to That Seen With Teclistamab in R/R Myeloma

Sundar Jagannath, MBBS

In a matching-adjusted indirect comparison, linvoseltamab elicited efficacy outcomes equivalent to those seen with teclistamab-cqyv (Tecvayli) in patients with triple-class–exposed, relapsed/refractory multiple myeloma, according to findings presented at the 2024 ASCO Annual Meeting.

“To date, there are no head-to-head clinical trials comparing the effectiveness of linvoseltamab vs teclistamab. Here, we compare linvoseltamab and teclistamab in relapsed/refractory multiple myeloma using a matching-adjusted indirect comparison approach that accounts for cross-trial differences by balancing reported prognostic factors between trials,” study author Sundar Jagannath, MBBS, director of the Center of Excellence for Multiple Myeloma and professor of Medicine at the Mount Sinai Tisch Cancer Institute, said in a presentation of the data.

Jagannath and fellow authors conducted a systematic literature review, as well as a search in conference presentations and abstracts, on data regarding the clinical efficacy on patients with triple-class exposed myeloma. Ultimately, they compared data from two trials: the phase 1/2 LINKER-MM1 trial (NCT03761108), which included patient-level data for patients receiving a full 200-mg dose of linvoseltamab, and the phase 1/2 MajesTEC-1 trial (NCT03145181, NCT04557098), which tested teclistamab in relapsed or refractory myeloma. Patients from LINKER-MM1 who were previously treated with a BCMA-targeted antibody-drug conjugate were excluded from the analysis to align with the patient population in the MajesTEC-1 trial.

The researchers then compared objective response rates (ORR) per independent review committee (IRC), very good partial response (VGPR) per IRC, complete response (CR) or better per IRC, minimal residual disease (MRD) negativity rates, duration of response (DOR) per IRC, progression-free survival (PFS) per IRC, and overall survival (OS) per IRC. Researchers included the exploratory outcome of time to next treatment (TTNT).

Data from the LINKER-MM1 trial were weighed to match the key baseline characteristics in the MajesTEC-1 trial, including cytogenetic risk, age, refractory status, ISS score, ECOG performance status, and extramedullary disease/plasmacytoma status. These variables were considered as Group A, or the most important variables. Other prognostic factors considered included creatinine clearance, lactate dehydrogenase, number of prior lines of therapy, prior autologous stem cell transplant, time since diagnosis, hemoglobin levels, and sex.

In particular, this analysis included 107 patients from the LINKER-MM1 trial with a median follow-up of 11 months and 150 patients from the MajesTEC-1 trial with a median follow-up of 9.8 months.

Before matching based on baseline characteristics and available prognostic factors, linvoseltamab showed better efficacy compared to teclistamab in all outcomes.

After matching on the Group A prognostic factors, rates of complete response (45% vs 32%; OR = 1.74; 95% CI, 1.17-2.59), progression-free survival (not reached [NR] vs 10.10 months; OR = 0.52; 95% CI, 0.33-0.83), and time to next therapy (NR vs NR; OR = 0.49; 95% CI, 0.29-0.84) continued to be significantly higher with linvoseltamab compared with teclistamab. In addition, the overall response rate (72% vs 63%; OR = 1.54; 95% CI, 0.99-2.38), MRD negativity (19% vs 13%; OR = 1.50; 95% CI, 0.82-2.76), duration of overall survival (NR vs 18.27 months; OR = 0.75; 95% CI, 0.44-1.28), and duration of response (NR vs NR; OR = 0.87; 95% CI, 0.41-1.86) were numerically improved with linvoseltamab vs teclistamab.

A second analysis was performed that matched data on all available prognostic factors, which showed consistent results. Compared with teclistamab, progression-free survival was significantly longer with linvoseltamab (NR vs 10.10 months; OR = 0.58; 95% CI, 0.34-0.99). It also showed numerically favorable overall survival (NR vs 18.27 months; OR = 0.82; 95% CI, 0.45-1.50), time to next therapy (NR vs NR; OR = 0.63; 95% CI, 0.35-1.12), overall response rate (71% vs 63%; OR = 1.49; 95% CI, 0.91-2.43), and the rates of complete response (42% vs 32%; OR = 1.56; 95% CI, 1.00-2.43) and MRD negativity (OR = 1.31; 95% CI, 0.67-2.56). By comparison, duration of response (NR vs NR; OR = 1.19; 95% CI, 0.49-2.89) and the rate of VGPR or better (59% vs58%; OR = 0.97; 95% CI, 0.63-1.57) were numerically favorable for teclistamab vs linvoseltamab.

“In conclusion, this matching-adjusted indirect comparison showed that linvoseltamab numerically improved most efficacy outcomes vs teclistamab, with progression-free survival reaching statistical significance,” Jagannath said.

According to the presentation, an updated analysis will be presented at the European Hematology Association 2024 Congress.

Reference

Jagannath S, Lee HC, Richter J, et al. Indirect comparison of linvoseltamab versus teclistamab for triple-class refractory (TCE) relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2024;42 (suppl 16):7560. doi:10.1200/JCO.2024.42.16_suppl.7560