Oncology Advances: Long-Term Efficacy and Safety Results on Talquetamab Treatment for Patients With R/R Multiple Myeloma

According to updated long-term follow-up data, bispecific antibody talquetamab continues to demonstrate deep and durable responses and no new safety signals among patients with relapsed/refractory (R/R) multiple myeloma (MM).

Talquetamab targets novel antigen G protein-coupled receptor family C group 5 member D (GPRC5D), which is expressed in malignant plasma cells. Talquetamab is the first GPRC5D-targeting bispecific antibody approved in the US for the treatment of patients with R/R MM. 

In earlier results from MonumenTAL-1, which enrolled patients with R/R MM who were both naive and exposed to prior T-cell redirection therapy (TCR), the overall response rates (ORR) were shown to be >71% in patients naive to TCR, and 65% in patients with prior TCR at the approved subcutaneous (SC) doses of 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W). Early onset of GPRC5D-related adverse events, including dysgeusia, were found to be associated with a higher likelihood of response; prior data support flexibility to adjust talquetamab dosing in responders to mitigate adverse events while maintaining efficacy. An exposure-response relationship was observed for grade 1 or 2 dysgeusia; however, rates were found to be similar at both approved doses.

At the European Hematology Association (EHA) 2024 Congress in Madrid, Spain, Dr. Leo Rasche, MD, University Hospital of Wurzburg, Wurzburg, Germany, presented updated results from the MonumenTAL-1 trial on the long-term efficacy and safety of talquetamab for these patients. Long-term follow-up results of patients receiving talquetamab at the approved doses show that as of January 29, 2024, ORR was demonstrated to be 74% in the QW group, 70% in the Q2W group, and 67% for patients in the prior TCR cohorts. ORR was found to be consistent across high-risk subgroups, except for patients with extramedullary disease, who demonstrated lower ORR. As for the group of patients with prior TCR, ORR was 71% for those with prior chimeric antigen receptor (CAR) T-cell therapy and 58% for those with prior bispecific antibody therapy.

For each of these groups, the median time to first response was found to be 1.2 in the QW, 1.3 in the Q2W, and 1.2 months in the TCR group, respectively; the median time to very good partial response (VGPR) as best response was recorded as 2.2, 2.3, and 1.8 months; to complete response (CR) or better as best response was 3.0, 5.8, and 2.7 months, respectively. Better durability was observed in the Q2W versus the QW cohort. For patients with prior TCR, the median PFS demonstrated was 12.3 months with prior CAR T-cell therapy and 4.1 months with prior bispecific antibody therapy.  Within the Q2W cohort, 40% of patients achieved ≥CR, most by approximately 1 year, although a ≥CR may take longer to achieve. Patients who displayed  deeper also responses showed a lengthier duration of response.

These updated 2024 results show a safety profile which matches with previous results, including no new safety signals. Early evident weight loss was evaluated according to patient vital signs, and was recorded in 39% of QW patients, 34% of Q2W patients, and 39% of prior TCR patients. This weight loss generally was recognizable early in treatment, before stabilizing and improving over time. There was no increase in grade 3 or 4 infections observed with longer follow-up. Study authors also noted that modest intravenous immunoglobulin was required in 16%, 14%, and 24% of patients, respectively.

GPRC5D-associated adverse events led to few dose reductions and discontinuations, and only 1 additional patient discontinued treatment since the previous report. Results show that overall rates of dose reductions (15%, 10%, and 12%) and discontinuations (5%, 10%, and 5%,) due to treatment-related adverse events remained low, including no treatment-related deaths.

 Source:

Rasche L, Schinke C, Touzeau C, et al. Long-term efficacy and safety results from the phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients With relapsed/refractory multiple myeloma. Presented at European Hematology Association (EHA) 2024 Hybrid Congress. June 13–16, 2024. Madrid, Spain.