LimiTec

Results: As of 7/15/2025, 43 pts (median age 73 yrs (range 43-92); 21 male; 25 White, 14 Black, 4 Hispanic) enrolled. 18/43 (42%) had ≥1 and 7/43 (16%) ≥2 high risk cytogenetic abnormalities (defined as del17p, t(14;16), t(4;14), 1q gain/amp). Median prior lines of therapy was 4 (range 2-13) with 95% triple-class and 44% penta-drug refractory. 10/43 (23%) had ≥1 prior BCMA-directed therapies (BCMA-DT) (4 bela-maf, 2 cilta-cel, 6 ide-cel). Median time from diagnosis to Tec initiation was 7.1 years (range 1-14.8). Median time from first full Tec dose to enrollment was 7.3m (range 5.7-9.5). Response to Tec at enrollment was VGPR in 72% (71% of which met serum/urine criteria for CR) and ≥CR in 28%. Median potential follow-up by reverse K-M is 10.6m (95% CI 7.2-15.6). 6 pts have met failure criteria (1 died due to PD before resuming Tec, 5 failed to respond to Tec re-treatment after PD). 4 additional pts have resumed Tec for PD and are pending response assessment; these 4 pts are counted as failures in this interim analysis. Estimated FFP at 6m post-enrollment is 77% (95% CI 64-92) and at 12m is 73% (95% CI 60-90). Similar outcomes were observed in pts with prior BCMA-DT (6m FFP 88%, 12m 70%) and <CR by serum/urine criteria (6m FFP 69%, 12m 69%).

Among 5 pts who resumed Tec and failed to respond, 4 had BMB at PD with BCMA immunohistochemistry: 1 had no detectable MM, 1 with PD at 14.6m post-enrollment had 5% plasma cells (PCs) that were BCMA+, and 2 with PD at 5.0m and 5.9m post-enrollment had 30% and 80% PCs that were BCMA-neg by IHC. BCMA gene sequencing on CD138-selected cells from the BMB with 30% BCMAneg MM showed loss of the entire BCMA coding region and two BCMA splice-site mutations, indicating selection for multiple BCMA-neg clones. 3/3 pts with PD who received talquetamab (Tal) as next therapy responded (2 VGPR, 1 CR). Among all pts with evaluable samples, plasma soluble BCMA (sBCMA) gradually rose through 6m post-enrollment but remained at low end of normal range (median 2.3 ng/mL, IQR 1.6-3.7, at 6m) including in 4 samples collected at PD.

Conclusions: In this preliminary analysis, discontinuation of Tec after 6-9m yields outcomes comparable to historical expectations with continuous therapy with estimated median FFS of 73% at 12m postdiscontinuation in a cohort with 23% prior BCMA-DT. Early instances of PD (<6m after Tec discontinuation) that were evaluable exhibited BCMA loss and were thus unlikely due to Tec discontinuation. Response to Tal immediately after failing Tec re-treatment and low sBCMA at PD further suggest resistance due to BCMA loss/mutation as an important mechanism of PD even months after Tec discontinuation.