Real-World bispecific antibody therapy for Multiple Myeloma: Insights from Dutch Nationwide registry
Bispecific antibodies (BsAbs) are approved for treating relapsed or refractory multiple myeloma (RRMM) after three or more prior lines of therapy (LOT), if triple class exposed (TCE). Real-world data are crucial to assess their effectiveness and safety outside clinical trials.
This nationwide multicenter observational study collects real-world data on teclistamab (TEC; anti-BCMA) and talquetamab (TAL; anti-GPRC5D) for RRMM patients in a compassionate use program. It focuses on infection occurrence, preventive measures, treatment schedule adjustments, and quality of life (QoL) data collected at multiple intervals using EORTC QLQ-C30 and QLQ-MY20 questionnaires.
As of October 8th, 2024, 259 RRMM patients received TEC and 22 received TAL across 25 hospitals in the Netherlands. Currently, 113 patients are included in the registry. Patients had 2 to 12 prior LOT (median 4), all were TCE, and 69% were triple class refractory. Four patients had prior BCMA CAR-T treatment, and nine were treated sequentially with TEC and TAL. Seven patients did not start BsAb therapy due to rapid disease progression.
Analysis of 88 TEC-treated patients showed an ORR of 64%, with 56% achieving at least VGPR, at a median follow-up of 6.4 months. Three RRMM patients with secondary AL amyloidosis achieved rapid CR, ongoing at 8.0 months of median follow-up. Patients previously treated with BCMA CAR-T or TAL had an 86% ORR, at a median follow-up of 10.3 months. CRS and ICANS were reported in 60% and 8% of patients, respectively, mostly grade 1-2, with one likely death due to severe CRS. Tocilizumab was given to 47% of patients with CRS. Inflammatory pain flare occurred in 12% of patients, grade 3 in 9%. Infections occurred in 60% of patients, grade 3 in 34%. Prophylactic IVIG and antibiotics were given to 70% and 90% of patients, respectively. All patients started treatment with a standard step-up dosing schedule, followed by weekly administrations. The TEC dosing intervals were extended in 33% (biweekly), 27% (four-weekly), 2% (six-weekly), and 4% (eight-weekly). Therapy was discontinued in 54% of patients: 35% due to progressive disease and 19% due to toxicity, with 60% of those still responding at a median follow-up of 7.3 months.
Seven patients treated with TAL had an ORR of 71%, with 14% achieving at least VGPR, at a median follow-up of 14 months.
QoL data are limited but expanding. Updated efficacy, safety data, and long-term outcomes will be presented at the meeting.
This nationwide registry of BsAb treatment in RRMM showed similar efficacy to clinical trials. Infectious complications were common, but hospitalization rates were lower, likely due to prophylactic measures and extended dosing intervals. QoL data collection will reveal the impact of these therapies on patients’ lives.