Bispecific Antibodies for Multiple Myeloma in the Real World: Lessons Learnt from a Nation-Wide Dutch Observational Registry
Authors: Appelman Marjolein , Oostvogels Rimke , Geerts Paulus A.F. , Franssen Laurens , Spek Ellen van der , Lil Heleen de , Rooijen Cleo van , Ypma Paula F , Roeloffzen Wilfried , Broijl Annemiek , Nijhof Inger S. , Wester Ruth 
Published: December 2024

Background
Bispecific antibodies (BsAbs) targeting BCMA or GPRC5D have recently been approved for the treatment of relapsed or refractory multiple myeloma (RRMM) after three or more prior lines of therapy (LOT), if triple class exposed (TCE), and offers these patients a novel and effective therapy. Real-world data are critical to evaluate effectiveness and safety outside the well-defined clinical trial populations and to guide future improvements in the clinical use of these agents.
Methods
In this nationwide multicenter observational study, we retrospectively and prospectively collect real world data on teclistamab (TEC; anti-BCMA) and talquetamab (TAL; anti-GPRC5D) treatment offered to RRMM patients in a compassionate use program. We focus on the occurrence of infections during treatment, the use of preventive measures for infectious complications and adjustments in treatment schedules. Furthermore, for prospectively included patients, quality of life (QoL) data are collected since early 2024 at defined time points using the EORTC QLQ-C30 and QLQ-MY20 questionnaires. To our knowledge, these data have not been reported yet in a real-world setting.
Results
At data cut-off, June 28th, 2024, 261 RRMM patients were planned for BsAb treatment in the Netherlands outside of clinical trials, across 24 hospitals ranging from large (academic) centers to small community hospitals. Of these, 240 (92%) received TEC and 21 (8%) TAL. We aim to include &gt;80% of all treated patients in the Netherlands in the registry during the coming months, data will be updated at ASH.
Patients had received 3 to 12 (median 4) prior LOT, all patients were TCE and 71% of patients were triple class refractory. Four patients had previously been treated with BCMA CAR-T cells and six were sequentially treated with both TEC and TAL. Six patients were planned to start BsAb therapy, but did not actually receive treatment, in most cases due to rapid disease progression.
The overall response rate (ORR) in the 80 fully analyzed patients was 61%, with 41% ≥VGPR, and a median duration of response of 8.7 months at a median follow-up of 3.8 months. Three patients with RRMM and secondary AL amyloidosis started TEC treatment, all achieved a rapid CR that is ongoing at a median follow-up of 8.8 months. In patients previously treated with either BCMA CAR-T cells or TAL the response rate to TEC was 75%, with median duration of response of 7.9 and 8.6 months, respectively.
CRS and ICANS were reported in 61% and 8% of patients respectively, all grade 1-2. 41% of patients that experienced CRS received tocilizumab. Fifteen percent of patients experienced an inflammatory pain flare during cycles 1-2, which was grade 3 in 9%. Fifty percent of patients developed at least one infectious complication during BsAb treatment, which was grade 3 in 32%. To prevent infections, 73% of patients received prophylactic IVIG, and prophylactic antibiotics and vaccinations (for covid-19, influenza, pneumococcus and herpes zoster) were common. All patients started treatment with a standard step-up dosing schedule, followed by weekly administrations for teclistamab or biweekly administrations for talquetamab. The dosing interval of teclistamab was prolonged to biweekly, triweekly, four-weekly and eight-weekly administrations in 42%, 2%, 13% and 2% of patients respectively. Therapy was permanently discontinued in 55% of evaluable patients: 41% stopped because of progressive disease and 14% because of toxicity. Of the patients who stopped because of toxicity, response is currently ongoing in 60% at a median follow-up of 7.3 months.
QoL data are still limited in the current cohort, but are now rapidly expanding. Efficacy and safety data and longer-term outcomes will be shared at the meeting.
Conclusion
This nationwide observational study of BsAb treatment in RRMM showed similar efficacy data compared to the MajesTEC-1 and MonumenTAL-1 clinical trials and previously reported real-world datasets. Infectious complications are common with BsAbs, however a lower rate of hospitalizations for infections was observed in comparison to prior TEC cohorts, possibly due to the widespread use of prophylactic measures and the common prolongation of dosing intervals. QoL data are now collected, which will teach us about the impact of these novel therapies on patients' lives.