Talquetamab Shows Promise as Novel Agent for Patients With Multiple Myeloma

The novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, demonstrates substantial activity against multiple myeloma (MM) cell lines and primary MM cells, according to study findings.

The study, by Christie P.M. Verkleij, MD, Cancer Center Amsterdam, The Netherlands and collogues, sought to further enhance understanding of GPRC5D expression by measuring GPRC5D cell surface expression on MM cells from patients in different stages of the disease, as well as on normal plasma cells and other immune cell subsets. Moreover, they assessed the preclinical activity of talquetamab in MM cell lines and in fully autologous bone marrow samples obtained from patients with MM.

They also specifically investigated the potential impact of previous therapy, as well as several host and tumor characteristics, on T-cell redirection therapy with talquetamab.

Researchers evaluated cell surface expression of GPRC5D in bone marrow aspirates obtained from patients with newly diagnosed MM and primary plasma cell leukemia, patients with daratumumab-naïve relapsed/refractory MM, and patients with daratumumab-refractory MM. Normal bone marrow was acquired from age-matched patients undergoing cardiothoracic surgery.

In these samples, researchers simultaneously evaluated several other tumor characteristics and immune cell composition. Ex vivo efficacy of talquetamab was evaluated when bone marrow samples contained at least 2% MM cells and sufficient material was available. The samples were examined within 24 hours after bone marrow aspiration.

The study found that talquetamab effectively kills GPRC5D+ MM cell lines in the presence of T cells from both healthy donors or heavily pretreated patients with MM. In addition, talquetamab has potent anti-MM activity in bone marrow samples from 45 patients, including those with high-risk cytogenetic aberrations. No difference in talquetamab-mediated killing of MM cells from newly diagnosed, daratumumab-naïve relapsed/refractory (median of 3 prior therapies), and daratumumab-refractory (median of 6 prior therapies) patients were noted.

“In conclusion, we show that the GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab is a promising novel antimyeloma agent,” concluded Dr Verkleij and colleagues.

“These results provide the preclinical rationale for ongoing studies with talquetamab in relapsed/refractory MM,” they added.

Source:

Verkleij CPM, Broekmans MEC, van Duin M, et al. Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma. Blood Adv. 2021;5(8):2196-2215. doi:10.1182/bloodadvances.2020003805