(PA-035) Clinical Outcomes After Teclistamab Failure in Relapsed/Refractory Multiple Myeloma

Teclistamab (Tec) is a BCMAxCD3 bispecific antibody approved for triple-class exposed (TCE) relapsed or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOT). The optimal management of patients who relapse after teclistamab remains undefined. This is the first comprehensive study to characterize relapse patterns, salvage treatments and outcomes in RRMM patients progressing after Tec.


Methods:

We retrospectively analyzed 191 patients treated with Tec, 60 on clinical trials (Feb 2019–Feb 2023) and 131 commercially (Dec 2022–Apr 2024). Data cutoff was Mar 2025. Outcomes were comparable across cohorts, so analyses were pooled. Among Tec relapsed or refractory patients, we assessed disease characteristics, relapse types, salvage regimens, and outcomes. Treatment refractoriness was defined as less than partial response (< PR) after 2 treatment cycles. Progression was defined per 2016 IMWG criteria. Median follow-up from first salvage was 21.7 months (95% CI: 20.3–NE).


Results:

109 patients (57%) progressed after Tec, including 41 (68%) in the trial cohort and 68 (52%) in the commercial cohort. Of these, 52 (33 trial, 19 commercial) completed at least 1 full Tec cycle and received systemic salvage therapy and were included in this analysis. Median prior LOT was 6 (IQR 5–8.5); all were TCE, 83% were penta-exposed, and 21% had prior BCMA therapy (ide-cel: 7, belantamab: 4). Relapse types were biochemical (69%), end-organ damage (CRAB, 12%), and extramedullary disease (EMD, 19%). Notably, 50% of CRAB and 67% of EMD relapses were oligo- or non-secretory (defined as M-spike < 0.5 g/dL and involved free light-chain < 100 mg/L). Median overall survival from first salvage (OS2) was 11.3 months (95% CI: 7.3–14.2); median duration of response (DOR) was 3.2 months (95% CI: 1.9–5.7). The overall response rate (≥PR) to first salvage was 35%. Response rates and durability varied by regimen, with higher DOR observed in patients receiving novel agents such as talquetamab, other BCMA-directed therapies, or clinical trials. Achieving ≥PR to salvage therapy was associated with longer OS2 (HR: 0.3, P=0.006) and DOR (HR: 0.1, P< 0.001). Early relapse (< 6 months) predicted inferior OS2 (HR: 2, P=0.04). Other factors—including frailty (IWMG simplified frailty score), cytogenetic risk, penta-exposure, Tec refractoriness, and CRAB/EMD relapse—were not significantly associated with OS2 or DOR. In penta-exposed patients who progressed after Tec, the use of novel immunotherapies (CAR-T, BiTEs, ADCs) in salvage regimens was linked to prolonged DOR (HR: 0.4, P=0.04), though not OS2.


Conclusions:

This is the first real-world analysis of patients with RRMM who progressed after Tec. Prognosis is poor, especially with early Tec relapse (< 6 months). While no standard salvage exists, novel immunotherapies may offer improved disease control. These findings provide a key benchmark in a setting with limited prospective data.