Contributions
Abstract: EP967
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
B-cell maturation antigen (BCMA, CD269), a single transmembrane protein that is selectively expressed in the B-cell lineage, is a validated target for multiple myeloma (MM). BCMA can exists as both a surface protein and as a free soluble form (sBCMA). γ-secretase activity at the transmembrane domain leads to a shed BCMA protein fragment of approximately 6 kilodalton that can exist as free circulating sBCMA in blood. Teclistamab, a BCMA x CD3 bispecific antibody, and talquetamab, a GPRC5D x CD3 bispecific antibody, were developed to recruit CD3+ T cells to BCMA+ or GPRC5D+ MM cells, respectively.
Aims
The objective of this study was to evaluate sBCMA levels in response to treatment with teclistamab or talquetamab in patients with relapsed and/or refractory MM.
Methods
Serum samples from patients with relapsed and/or refractory MM enrolled in the teclistamab and talquetamab phase 1 studies (64007957MMY1001 and 64407564MMY1001, respectively) were collected (at various timepoints between baseline and cycle 4 or end of treatment) and analyzed for sBCMA by an electrochemiluminescence ligand binding assay. Soluble BCMA data were quantitatively analyzed in reference to the patient’s tumor burden and response, as well as to pharmacokinetic data. All patients enrolled in the phase 1 studies provided written informed consent.
Results
Teclistamab and talquetamab modulated levels of sBCMA in patients with high (≥ 50%) and low (< 50%) frequency of tumor plasma cells (TPCs), as well as in high and low risk cytogenetic groups. In cycle 3, the majority of the responders had reductions in sBCMA compared to baseline: 88% (50 out of 57) for teclistamab and 98% (49 out of 50) for talquetamab. In contrast, non-responders (patients who had progressive disease, stable disease, or minimal response) seemed to show an increase in sBCMA compared to baseline: 80% (33 out of 41) for teclistamab and 49% (24 out of 49) for talquetamab. Patients with deep responses tended to have a higher magnitude of sBCMA reduction compared to others. Based on the few patients who initially responded to teclistamab or talquetamab but then relapsed, sBCMA seemed to have an initial reduction followed by an increase in the levels. Soluble BCMA correlated with % bone marrow TPCs. The majority of patients with plasmacytoma (limited data were available) seemed to have high sBCMA, suggesting that sBCMA could be a comprehensive marker for tumor burden. Preliminary teclistamab population pharmacokinetic analysis showed that sBCMA did not appear to impact teclistamab exposure, suggesting that sBCMA was not acting as a sink for teclistamab.
Conclusion
Teclistamab and talquetamab induced changes in sBCMA levels that correlated with clinical activity, further supporting clinical development of these bispecific antibodies. Lastly, the findings provide support for sBCMA as a potential surrogate marker of myeloma tumor burden, and as a valuable marker for response in patients with MM.
Keyword(s): B-cell maturation antigen, Multiple myeloma
Abstract: EP967
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
B-cell maturation antigen (BCMA, CD269), a single transmembrane protein that is selectively expressed in the B-cell lineage, is a validated target for multiple myeloma (MM). BCMA can exists as both a surface protein and as a free soluble form (sBCMA). γ-secretase activity at the transmembrane domain leads to a shed BCMA protein fragment of approximately 6 kilodalton that can exist as free circulating sBCMA in blood. Teclistamab, a BCMA x CD3 bispecific antibody, and talquetamab, a GPRC5D x CD3 bispecific antibody, were developed to recruit CD3+ T cells to BCMA+ or GPRC5D+ MM cells, respectively.
Aims
The objective of this study was to evaluate sBCMA levels in response to treatment with teclistamab or talquetamab in patients with relapsed and/or refractory MM.
Methods
Serum samples from patients with relapsed and/or refractory MM enrolled in the teclistamab and talquetamab phase 1 studies (64007957MMY1001 and 64407564MMY1001, respectively) were collected (at various timepoints between baseline and cycle 4 or end of treatment) and analyzed for sBCMA by an electrochemiluminescence ligand binding assay. Soluble BCMA data were quantitatively analyzed in reference to the patient’s tumor burden and response, as well as to pharmacokinetic data. All patients enrolled in the phase 1 studies provided written informed consent.
Results
Teclistamab and talquetamab modulated levels of sBCMA in patients with high (≥ 50%) and low (< 50%) frequency of tumor plasma cells (TPCs), as well as in high and low risk cytogenetic groups. In cycle 3, the majority of the responders had reductions in sBCMA compared to baseline: 88% (50 out of 57) for teclistamab and 98% (49 out of 50) for talquetamab. In contrast, non-responders (patients who had progressive disease, stable disease, or minimal response) seemed to show an increase in sBCMA compared to baseline: 80% (33 out of 41) for teclistamab and 49% (24 out of 49) for talquetamab. Patients with deep responses tended to have a higher magnitude of sBCMA reduction compared to others. Based on the few patients who initially responded to teclistamab or talquetamab but then relapsed, sBCMA seemed to have an initial reduction followed by an increase in the levels. Soluble BCMA correlated with % bone marrow TPCs. The majority of patients with plasmacytoma (limited data were available) seemed to have high sBCMA, suggesting that sBCMA could be a comprehensive marker for tumor burden. Preliminary teclistamab population pharmacokinetic analysis showed that sBCMA did not appear to impact teclistamab exposure, suggesting that sBCMA was not acting as a sink for teclistamab.
Conclusion
Teclistamab and talquetamab induced changes in sBCMA levels that correlated with clinical activity, further supporting clinical development of these bispecific antibodies. Lastly, the findings provide support for sBCMA as a potential surrogate marker of myeloma tumor burden, and as a valuable marker for response in patients with MM.
Keyword(s): B-cell maturation antigen, Multiple myeloma