Talquetamab in Relapsed/Refractory multiple myeloma with renal impairment: A quaternary cancer center experience Free

Introduction Patients with relapsed/refractory multiple myeloma (RRMM) and renal impairment (RI) represent a high-risk group frequently excluded from clinical trials. Talquetamab (Tal), a GPRC5D-targeting bispecific antibody, received FDA approval in August 2023, upon achieving high efficacy and a favorable safety profile in the MonumenTAL-1 clinical trial, but data in RI populations is almost nonexistent. This analysis evaluates the safety and efficacy of Tal in RRMM patients treated at our quaternary cancer center with and without RI, including those with severe RI and dialysis dependence.

Methods In this study,36 RRMM patients were treated with Tal at our center, stratified into two primary cohorts: RI (CrCl <40 mL/min) (n=12, 33.3%) and no RI (n=24, 66.7%), with further subsets defined as severe RI (CrCl of <30 mL/min) (n=7, 19.4%) and dialysis-dependent (n=5, 13.9%). Baseline demographics, cytogenetics, treatment refractoriness, and adverse events were compared using the χ² or Fisher's exact test for categorical variables, and the Mann-Whitney U test for continuous variables. Efficacy outcomes are assessed between groups, and survival outcomes are evaluated using the Kaplan-Meier method and the log-rank test for comparison. A p-value of <0.05 indicated statistical significance.

Results Baseline demographics were generally balanced between RI and No RI groups, including age, gender, and race. Patients with RI had a higher incidence of high-risk cytogenetics (66.7% vs. 20.8%, p=0.03). The median number of prior lines of therapy in RI vs. No RI was (6 vs. 7.5, p=0.31). Triple class refractory status was high for both groups (100% vs. 95.8%), penta-refractory was (91.7% vs. 75%), and those who received previous BCMA-directed therapy (83.3% vs. 87.5%).

The safety profile of Tal was comparable between cohorts. Any-grade cytokine release syndrome (CRS) and grade ≥3 CRS occurred in 66.7% and 8.3%, respectively, in both groups, with more grade 1 CRS observed in RI cohort (58.3% vs. 45.8%, p=0.73). Any-grade Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in (16.7% vs. 20.8%, p=1.0) of RI vs No RI patients, with grade ≥3 ICANS (8.3% vs. 12.5%, p=1.0). No significant difference in tocilizumab, steroid, or anakinra use for treatment between groups. The median inpatient stay for step-up dosing was (10 vs. 9 days, p=0.23). Infection rate in RI was (8.3% vs. 16.7%, p=0.65), and dysgeusia was reported in 83.3% of both groups. Skin-related events occurred in (75% vs. 58.3%, p=0.47), and nail-related events in (83.3% vs. 54.2%, p=0.14).

Efficacy outcomes of the best overall responses in RI vs. No RI cohorts include overall response rate (ORR) (66.7% vs. 54.2%, p=0.71), complete response or better (≥CR) (33.3% vs. 8.3%, p=0.04), very good partial response (VGPR) (25% vs. 8.3%, p=0.13), and partial response (PR) (8.3% vs. 37.5%, p=0.14). Disease progression as best response was less frequent in the RI group (8.3 vs. 20.8%, p=0.64).

Subgroup analyses showed that patients with severe RI (n=7) achieved a best ORR of 57.1%, ≥CR of 14.3%, with VGPR of 28%. Among dialysis-dependent patients (n=5), 80% achieved ORR to Tal, including 20% with CR and 40% with VGPR.

For survival outcomes, the median follow-up time for the entire cohort (n=36) was (7.3 months [95% CI: 4.5-10.5]). There is an observed trend of higher median overall survival (OS) in RI as not reached (NR) [95% CI: 10.38-NR] vs. No RI group of 8.71 months [95% CI: 3.25-NR]. However, the median progression-free survival (PFS) was significantly higher in the RI cohort of 8.48 months [95% CI: 7.49-NR] vs. No RI of 2.63 months [95% CI: 2.07-5.26] (p=0.006). No significant differences between severe RI or dialysis-dependent cohort vs. the No RI cohort, despite shorter survival curves in these subgroups.Conclusions Talquetamab demonstrates a favorable safety profile and efficacy outcomes in RRMM patients with renal impairment, including those with severe RI or dialysis dependence. Despite a higher burden of high-risk cytogenetics, the RI cohort exhibited deeper responses, reflected by significantly higher rates of ≥CR and PFS compared to those in the No RI cohort. These findings position talquetamab as a viable treatment option for RI patients who have been traditionally excluded from clinical trials. Prospective studies are warranted to validate these observations and confirm their inclusion in future prospective trials to maximize benefits in real-world settings.