(PA-004) Real-world Bispecific Antibody Therapy for Multiple Myeloma: Insights from Dutch Nationwide Registry

Bispecific antibodies (BsAbs) are approved for treating relapsed/refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOT), if triple-class exposed (TCE). Real-world data are crucial to assess efficacy and safety beyond clinical trials.

Methods:

This nationwide, multicenter observational study collects real-world data on teclistamab (TEC; anti-BCMA) and talquetamab (TAL; anti-GPRC5D) for RRMM patients treated in a compassionate use program, focusing on infection occurrence, prophylactic measures, treatment schedule modifications, and quality of life (QoL) using EORTC QLQ-C30 and QLQ-MY20 questionnaires.

Results:

As of May 28, 2025, 337 RRMM patients received TEC and 39 received TAL across 28 hospitals in the Netherlands. Currently, 182 patients are included in the registry, with a median of 4 prior LOT, all TCE, and 71% were triple-class refractory. Four patients had prior BCMA CAR-T therapy and 29 received sequential TEC/TAL. Seven patients could not initiate BsAb therapy due to rapid disease progression and 44% would not have met MajesTEC-1 or MonumenTAL-1 trial eligibility.
Among 156 TEC-treated patients, the overall response rate (ORR) was 65%, with 57% achieving at least a very good partial response (≥VGPR) at 7.7 months median follow-up. Median progression-free survival (mPFS) was 11.9 months; among trial-ineligible patients, mPFS was 8.1 vs. 16.0 months in eligible patients. The median duration of response was not reached at 15.8 months follow-up, with 58% maintaining response at 24 months. Among seven patients with secondary AL amyloidosis, 86% achieved ≥VGPR at a median follow-up of 15.7 months. Patients previously treated with BCMA CAR-T therapy had an ORR of 50%, while those previously treated with TAL had an ORR of 80%.

CRS and ICANS were reported in 51% and 6% of patients, respectively, mostly grade 1-2, with one fatal CRS case. Tocilizumab was administered to 41% of patients with CRS. Inflammatory pain flare occurred in 13%. Infections were observed in 64% of patients (grade ≥3 in 46%), IVIG and antibiotic prophylaxis in 89% and 90% of patients, respectively.

TEC dosing intervals were extended at six months in 39% (biweekly), 13% (four-weekly), 3% (six-weekly), and 3% (eight-weekly), and at one year in 50% (biweekly), 5% (three-weekly), 19% (four-weekly), 2% (six-weekly), and 7% (eight-weekly).

Among 21 TAL-treated patients, the ORR was 71%, with 48% achieving ≥VGPR at a median follow-up of 6.5 months, with mPFS 4.8 months. Patients previously treated with TEC had an ORR of 65% with TAL, with 53% achieving at least VGPR at 5.0 months of follow-up.

Conclusions:

The response rates and PFS observed in this real-world registry align with clinical trial outcomes, reinforcing the effectiveness of these treatments in broader clinical practice. Infectious complications were frequent, but hospitalization rates were lower, likely due to prophylaxis and adjusted dosing. Ongoing QoL data collection will provide further insights into the impact of these therapies.