A Real-World Analysis of the Safety and Efficacy of Teclistamab for Patients with Relapsed/Refractory Multiple Myeloma and Baseline Renal Impairment
Authors: Habib Alma , Khan Abdullah Mohammad , Laharwal Mehak M , Mewawalla Prerna , McKenna Marshall , Tiger Yun Kyoung , Shaikh Hira , Strouse Christopher , Green Kimberly M , Davis James A , Hashmi Hamza , Snyder Jordan , Mahmoudjafari Zahra , Mushtaq Muhammad Umair , Ahmed Nausheen , Abdallah Al-Ola , Atrash Shebli , Paul Barry , Friend Reed 
Published: December 2024

Introduction: In the pivotal clinical trial (MajesTEC-1), teclistamab-cqyv (Tec), a bispecific B-cell maturation antigen (BCMA)-directed T-cell engager, showed promising efficacy in terms of overall response rate and duration of response in heavily pretreated relapsed refractory multiple myeloma (RRMM); however, patients (pts) with an estimated glomerular filtration rate of &lt;40mL/min were excluded. The effect of Tec in treatment of RRMM in pts with baseline renal impairment (RI) is limited. Herein, we evaluated the impact of baseline RI on development of toxicities and outcomes in RRMM following treatment with Tec.

Methods: We conducted a retrospective study of RRMM pts who received Tec at multiple academic institutions in collaboration with US Myeloma Innovations Research Collaborative (USMIRC). RI was defined as creatinine clearance of &lt;40 mL/min. Responses to therapy were evaluated using International Myeloma Working Group criteria. Adverse events were graded based on CTCAE v5.0 criteria. Using R Core Team (2024), descriptive analysis was performed. Continuous variables were summarized and reported mean (min, max) and median (IQR), and dichotomized factors by total numbers/frequency. Fisher's exact test was used to analyze contingency tables; Wilcoxon rank-sum test to compare two independent samples. Kaplan-Meier methods were used for progression-free (PFS).

Results: Between August 2022 and June 2024, 164 RRMM pts who received Tec were included; 58 (35%) pts had baseline RI and 106 (64.6%) pts had normal renal function (nRF). Median age at diagnosis was 68 (37-87), 41% were female, 20% were Black and 1.2% Hispanic. Pts with RI had higher rates of prior BCMA exposure (48% vs 31%, p=0.033) and triple refractory disease (88% vs 74%, p=0.032). Median prior lines of therapy were 5 (4-7) in RI and 6 (4-7, p=0.7) in nRF groups.

Of the evaluable 102 pts, 24 (57.1%) pts with RI and 25 (42%) with nRF experienced cytokine release syndrome (CRS). Grade (G) 1 CRS was most frequent in pts with RI, 50% vs 37% (p=0.3). Median onset and duration to CRS was 3 days (2-4 days, p=0.6) and 1 day (1-2 days, p=0.8) in both groups, respectively. In the RI group, 3 (7.1%) pts developed immune effector cell-associated neurotoxicity syndrome (ICANS) vs 6 (10%) pts with nRF; rates of G 3/4 ICANS were 0% vs 1% (p=0.5). Dexamethasone was required in 26% vs 33% (p=0.4) and tocilizumab in 29% vs 13% (p=0.056) in RI vs nRF.

All pts with RI were diagnosed with an infection (100% vs 0%, p=&lt;0.001), specifically severe infection (57%, p&lt;0.001), with median onset of 50 days (4-231, p=0.005). At 30-days, there were no differences in rates of G 3/4 neutropenia (18.8% vs 10%, p=0.4), thrombocytopenia (14.4% vs 15%, p=0.7), and anemia (7.1% vs 11.7%, p=&gt;0.9) similar to G 3/4 neutropenia (4.8% vs 5%, p=&gt;0.9), thrombocytopenia (2.4% vs 3.4%, p=0.7), and anemia (11.9% vs 8.4%) at 90-days in RI and nRF groups. There was no difference in liver toxicity (23.5% vs 23.7%, p=0.2), GI toxicity (4.8% vs 0%, p=0.2), neuropathy (2.4% vs 3.3%, p=&gt;0.9), or neutropenic fever (2.4% vs 0%, p=0.4). Pts with RI experienced more frequent dose delays (52% vs 22%, p=0.001) and were hospitalized for subsequent doses of Tec (50% vs 6.7%, p=&lt;0.001), but had comparable rates of ICU admissions during initial step-up dosing (2.4% vs 5.0%, p=0.6; odds ratio 3.39, p=0.127).

Overall response rate (ORR) was seen in 35% vs 75% (p=&lt;0.001) and ≥VGPR was achieved in 29% vs 54% (p=&lt;0.001) in RI and nRF, respectively. Median PFS in RI vs nRF was 8.87 (0.8-NR) vs 5.3 (3.7-12.8) months, (HR=1.33, p=0.3). For pts with RI, univariate analysis showed IMID refractory disease (HR &gt;5, p=0.044) and extramedullary disease (EMD; HR 3.48, p=0.059) to negatively impact PFS. In nRF, IMID refractory (HR 4.04, p=0.015), BCMA exposure in prior 6 months (HR 2.56, p=0.014), ECOG ≥2 (HR 2.47, p=0.003) and EMD (HR 2.11, p=0.001) showed similar effect on PFS. In multivariate analysis for PFS after adjusting for IMID refractory and EMD, response of VGPR or better remained significant (HR 0.10, p=&lt;0.001). 1-year survival rates for pts with RI was 49% vs 59% (p=0.032) in nRF.

Conclusions: RRMM pts with baseline RI treated with Tec exhibited no increased rates of CRS, ICANS, cytopenia, GI toxicity, neuropathy, or neutropenic fever; however, they did develop more infections compared to pts with nRF. Although there is comparable efficacy for pts with baseline RI in terms of PFS, closer monitoring is warranted due to pronounced infection rates.