A German multicenter real-world analysis of talquetamab in 138 patients with relapsed/refractory multiple myeloma

Abstract

Bispecific T-cell engagers (BTCEs) represent a paradigm shift in the treatment of relapsed/refractory multiple myeloma (RRMM). Talquetamab, a GPRC5DxCD3 BTCE, has shown promising results in the MonumenTAL-1 trial and was recently approved by the Food and Drug Administration and the European Medicines Agency. However, treatment under real-world conditions may not represent patient characteristics in clinical trials with restricted enrollment criteria. We performed a retrospective real-world analysis including 138 RRMM patients treated with talquetamab at 21 German centers. Of evaluable patients, 43% had ISS stage III, 37% had extraosseous disease, and 48% had high-risk cytogenetics. After a median of six prior therapy lines, 58% of patients would not have been eligible for MonumenTAL-1. With a median follow-up of 8.2 months, we observed an overall response rate of 65% and a median progression-free survival of 6.4 months (95% confidence interval 5.1-9.0). Prior BTCE exposure, ISS stage III, extraosseous disease, and penta-drug refractory disease were associated with unfavorable outcomes. Grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 5.1% and 1.5% of patients, respectively. In summary, our real-world study confirms the efficacy and safety of talquetamab, despite a high proportion of patient- and disease-related risk factors. These results support its use as bridging or long-term treatment, even in advanced stages.

Figure 1

Efficacy of talquetamab in the real‐world setting. (A) Cohort description and analysis workflow. The total real‐world cohort included 138 relapsed/refractory multiple myeloma (RRMM) patients who had received standard‐of‐care (SOC) talquetamab at one of 21 German centers. The safety analyses included all patients with available data, unless otherwise stated. The efficacy analyses included all evaluable patients who had received ≥1 full dose of talquetamab. Details on treatment application and status and loss to follow‐up are provided in Table S1. Patient and disease characteristics, safety, and efficacy were compared to the MonumenTAL‐1 study cohort of patients treated with subcutaneous talquetamab at a dose of 800 μg/kg every other week. (B) Comparison of response rates between the real‐world cohort and the MonumenTAL‐1 cohort. Kaplan–Meier estimates of (C) progression‐free survival (PFS), (D) duration of response (DOR), and (E) overall survival (OS). The median survival time in months and the 95% confidence interval (CI), the number of evaluable patients at risk and the number of events are provided below the curve. The light shading of the curve indicates the 95% confidence intervals. (F) Causes of a total of 46 deaths. The non‐relapse mortality (NRM) cases included three patients who died from sepsis, three patients who died from other malignancies or related complications, one patient who died from an esophageal rupture, and one patient who died from Stevens‐Johnson syndrome/toxic epidermal necrolysis. Another case of NRM due to an infection occurred after subsequent CAR T‐cell therapy and was therefore listed separately. CI, confidence interval; CR, complete response; DOR, duration of response; MR, minimal response; n.a., not available; nCR, near complete response; NE, not estimable; NRM, non‐relapse mortality; OS, overall survival; PD, progressive disease; PFS, progression‐free survival; PR, partial response; RRMM, relapsed/refractory multiple myeloma; s.c., subcutaneous; sCR, stringent complete response; SD, stable disease; SOC, standard of care; VGPR, very good partial response.

Figure 2

Baseline characteristics associated with treatment response, progression‐free survival (PFS), and overall survival (OS). Comparison of response rates between patients with no prior bispecific T‐cell engager (BTCE) therapy and patients with prior BTCE therapy (A), between patients with International Staging System (ISS) stages I and II and patients with ISS stage III before the first talquetamab dose (B), and between patients with no extraosseous disease (EOD) and with EOD before the first talquetamab dose (C). (D) Kaplan–Meier estimates of the probability of PFS for patients with no penta‐drug refractory disease (blue) and patients with penta‐drug refractory disease (red) (3‐month PFS 79% vs. 58%; 6‐month PFS 64% vs. 47%). (E) Kaplan–Meier estimates of the probability of PFS for patients with no EOD manifestations (blue) and patients with EOD manifestations (red) (3‐month PFS 78% vs. 44%; 6‐month PFS 68% vs. 25%). (F) Kaplan–Meier estimates of the probability of OS for patients with ISS stages I and II (blue) and patients with ISS stage III (red) (3‐month OS 98% vs. 82%; 6‐month OS 95% vs. 70%). (G) Kaplan–Meier estimates of the probability of OS for patients with no EOD manifestations (blue) and patients with EOD manifestations (red) (3‐month OS 93% vs. 85%; 6‐month OS 85% vs. 68%). The median survival times in months and the 95% confidence intervals (CI), the results of the Cox regression analysis (hazard ratio [HR] and 95% CI) and the log‐rank test, the number of evaluable patients at risk and the number of events are provided above or below the curves. BTCE, bispecific T‐cell engager; CI, confidence interval; CR, complete response; EOD, extraosseous disease; HR, hazard ratio; ISS, International Staging System; MR, minimal response; n.a., not available; nCR, near complete response; NE, not estimable; OS, overall survival; PD, progressive disease; PFS, progression‐free survival; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.