Linvoseltamab May Improve Outcomes Vs Teclistamab in R/R Multiple Myeloma

Linvoseltamab (Lynozyfic) showed statistically significant improvements in outcomes like progression-free survival (PFS) and duration of response (DOR) compared with teclistamab-cqyv (Tecvayli) among patients with triple-class–exposed relapsed/refractory multiple myeloma, according to a matching-adjusted indirect comparison (MAIC) analysis presented in a poster session at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO).

Prior to matching, an unadjusted analysis indicated that linvoseltamab demonstrated statistically significantly improved DOR, PFS, overall survival (OS), and time to next treatment (TTNT); overall response rate (ORR), very good partial response (VGPR) or better rate, and complete response (CR) or better rate numerically improved with linvoseltamab in this analysis. Similar statistically significant improvements and numerical improvements were observed when matching on 6 key predefined prognostic factors (effective sample size [ESS] = 82.5).

The median DOR was 24.0 months (95% CI, 18.7- not evaluable [NE]) with teclistamab and not reached (NR; 95% CI, 29.4-NE) with linvoseltamab per adjusted analysis (HR, 0.54; 95% CI, 0.31-0.92; P = .02). The DOR rates for teclistamab and adjusted linvoseltamab, respectively, were 70.2% (95% CI, 61.9%-79.5%) vs 86.7% (95% CI, 78.0%-96.5%) at 12 months and 49.4% (95% CI, 40.7%-60.1%) vs 67.2% (95% CI, 55.2%-81.9%) at 24 months.

The median PFS was 11.4 months (95% CI, 8.8-17.1) with teclistamab and NR (95% CI, 19.7-NE) for linvoseltamab when matching on key predefined prognostic factors (HR, 0.55; 95% CI, 0.36-0.82; P <.01). Across each group, the PFS rates were 48.8% (95% CI, 41.6%-57.1%) vs 69.3% (95% CI, 59.4%-80.9%) at 12 months and 34.3% (95% CI, 27.7%-42.6%) vs 55.8% (95% CI, 45.0%-69.2%) at 24 months.

Data showed a median OS of 22.2 months (95% CI, 16.1-30.6) with teclistamab and NR (95% CI, 23.8-NE) with linvoseltamab when matching for prognostic factors (HR, 0.64; 95% CI, 0.43-0.97; P = .04). The 12-month and 24-month OS rates across each group were 64.1% (95% CI, 57.2%-71.9%) vs 75.5% (95% CI, 66.6%-85.6%) and 49.0% (95% CI, 41.9%-57.4%) vs 60.4% (95% CI, 49.9%-73.1%), respectively.

The median TTNT was 12.6 months (95% CI, 9.2-17.6) with teclistamab and NR (95% CI, NE-NE) with linvoseltamab when adjusting for prognostic factors. TTNT rates in each group were 51.7% (95% CI, 44.6%-60.0%) vs 79.9% (95% CI, 71.3%-89.6%) at 12 months and 35.9% (95% CI, 29.2%-44.1%) vs 64.3% (95% CI, 54.1%-76.4%) at 24 months.

Based on independent review committee assessment, teclistamab produced an ORR of 63.0% (95% CI, 55.2%-70.4%), a VGPR or better rate of 59.4% (95% CI, 51.5%-67.0%), and a CR rate or better rate of 46.1% (95% CI, 38.3%-54.0%). The corresponding rates of teclistamab per adjusted analysis were 71.9% (95% CI, 61.1%-80.6%), 63.1% (95% CI, 52.1%-73.0%), and 50.8% (95% CI, 40.0%-61.6%). When matching for key prognostic factors, linvoseltamab showed improvements in ORR (OR, 1.50; 95% CI, 0.97-2.32; P = .07), VGPR or better rate (OR, 1.17; 95% CI, 0.79-1.74; P = .44), and CR or better rate (OR, 1.21; 95% CI, 0.83-1.76; P = .32).

“In the absence of head-to-head trials, MAICs following well-established methods offer benefits in understanding the relative efficacy of treatment options while adjusting for differences in trial population characteristics,” Hans C. Lee, MD, director of Multiple Myeloma Research at Sarah Cannon Research Institute, wrote with coauthors in the poster. “Results from the updated MAIC with longer [follow-up] are consistent with prior analyses, demonstrating statistically significant improvements for linvoseltamab vs teclistamab in DOR, PFS, OS, and TTNT. These findings with the longest available [follow-up] suggest continued greater efficacy for linvoseltamab vs teclistamab, highlighting its potential as a highly effective treatment option for patients with [triple-class–exposed relapsed/refractory multiple myeloma].”

Investigators conducted a systematic literature review to identify published efficacy data on teclistamab and linvoseltamab. Findings for linvoseltamab included patient-level data from the phase 1/2 LINKER-MM1 trial (NCT03761108) on those who received the agent at 200 mg. Aggregate data on teclistamab included findings from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098).

Outcomes of interest in the analysis included ORR, CR or better, VGPR or better, DOR, PFS, and OS; TTNT was considered an exploratory outcome. Investigators conducted one MAIC matching on the 6 predefined prognostic factors of cytogenetic risk, age, refractory status, ISS stage, ECOG performance status, and extramedullary disease or plasmacytoma status. Another MAIC matched patients on all 17 prognostic features in both trials.

According to the study investigators, the follow-up was shorter in the LINKER-MM1 trial vs the MajesTEC-1 study, which may have limited the assessment of time-to-event outcomes like DOR, PFS, OS, and TTNT. Additionally, residual confounding may have been present, and all analyses based on the expanded set of all variables had reduced ESS, introducing some uncertainty to the estimates.

Reference

Lee HC, Bumma N, Richter JR, et al. Comparative efficacy of linvoseltamab versus teclistamab in triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM): updated matching-adjusted indirect comparison (MAIC) with longer follow-up. J Clin Oncol. 2026;44(suppl 16):7526. doi:10.1200/JCO.2026.44.16_suppl.7526