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The following is a summary of “Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1–2 study,” published in the March 2025 issue of Lancet Hematology by Chari et al. 

Talquetamab, a GPRC5D × CD3 bispecific antibody, is approved for relapsed or refractory multiple myeloma. Phase 1 of MonumenTAL-1 showed its clinical activity at 0.4 mg/kg weekly and 0.8 mg/kg every 2 weeks. 

Researchers conducted a retrospective study to evaluate the safety, activity, and response duration of talquetamab, including in patients with prior T-cell redirection therapy (TCR), using a post-hoc analysis with longer follow-up at 0.8 mg/kg every 2 weeks. 

They conducted a multicentre, open-label, phase 1–2 study evaluating talquetamab. They assessed 0.4 mg/kg weekly and 0.8 mg/kg every 2 weeks in phase 2 for patients aged ≥18 years with ≥3 prior therapies, Eastern Cooperative Oncology Group status 0–2, and naive or exposed to TCR. The primary endpoint was the overall response rate by independent review in patients receiving ≥1 dose. Safety was assessed in all patients receiving ≥1 dose. 

The results showed that among 735 screened patients, 537 were treated, and 198 (27%) were excluded. As of Oct 11, 2023, 375 received talquetamab: 143 in the 0.4 mg/kg weekly group, 154 in the 0.8 mg/kg biweekly group, and 78 with previous TCR. Of these, 217 (58%) were male and 158 (42%) were female; 325 (87%) were White and 32 (9%) were Black. Median follow-up was 25.6 months (IQR 8.5–25.9), 19.4 months (9.2–20.7), and 16.8 months (7.6–18.7), respectively. Overall response rates were 74% (106/143, 95% CI 66–81), 69% (107/154, 62–77), and 67% (52/78, 55–77). Common adverse events included cytokine release syndrome (113 [79%] of 143 patients, 115 [75%] of 154 patients, and 57 [73%] of 78 patients), taste changes (103 [72%], 110 [71%], and 59 [76%]), and infections (85 [59%], 105 [68%], and 59 [76%]). Grade 3–4 events included neutropenia (44 [31%], 33 [21%], and 37 [47%]), anaemia (45 [31%], 40 [26%], and 21 [27%]), and lymphopenia (37 [26%], 40 [26%], and 13 [17%]). Fatal events occurred in 5, 7, and 0 patients, none treatment related. 

Investigators observed high overall response rates in heavily pretreated patients with longer follow-up. Response was promising in previous patients with TCR, and adverse events (AEs) were common but led to few discontinuations. 

Source: thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00385-5/fulltext