Dima Danai, Afrough Aimaz, Goel Utkarsh, Grajales-Cruz Ariel F, Khouri Jack, Julian Kelley, Pasvolsky Oren, Banerjee Rahul, Razzo Beatrice, Ferreri Christopher J, Vazquez-Martinez Mariola A, Davis James A, Sannareddy Aishwarya, Castaneda Omar, Raza Shahzad, Portuguese Andrew J, Gaballa Mahmoud R, Rana Masooma S, Lieberman-Cribbin Alex, DeJarnette Shaun, Gonzalez Rebecca, Chen Anna, Herr Megan M, Mikkilineni Lekha, Hosoya Hitomi, Ouchveridze Evguenia, Kaur Gurbakhash, Rossi Adriana, Shune Leyla, Anwer Faiz, Lin Yi, Richard Shambavi, Sborov Douglas W, Baz Rachid C, Garfall Alfred L, Lee Hans C, Anderson Larry D, Cowan Andrew J, Patel Krina K, Voorhees Peter M, Sidana Surbhi, Hansen Doris K, Atrash Shebli, Susanibar-Adaniya Sandra P
Division of Hematology-Oncology, Fred Hutch Cancer Center, University of Washington, Seattle, WA.
Department of Hematology-Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, OH.
Blood Adv. 2025 Jul 22;9(14):3408-3417. doi: 10.1182/bloodadvances.2025016059.
Outcomes of bispecific antibodies in patients with renal impairment (RI) are not well characterized, given the exclusion of these patients from clinical trials. Herein, we evaluated patients with relapsed/refractory multiple myeloma and RI treated with standard-of-care teclistamab. RI was defined as creatinine clearance (CrCl) <40 mL/min. CrCl <30 mL/min or dialysis dependence was defined as severe RI. Of the 384 included patients, 81 (21%) had RI, including 45 (18%) with severe RI, and 18 (5%) on dialysis. Patients with RI were more likely to be older (median age, 71 vs 67 years; P = .002) and have a higher median number of previous lines of therapy (7 vs 6; P = .04). Rates and severity of cytokine release syndrome (51% vs 59%; grade ≥3: 1.2% vs 1%) and immune effector cell-associated neurotoxicity syndrome (16% vs 13%; grade ≥3: 2.5% vs 2.6%) were similar in patients with and without RI, respectively. Patients with RI had higher baseline and day 30 post-teclistamab grade ≥3 anemia and grade ≥3 thrombocytopenia. Renal function did not worsen after teclistamab initiation in most patients with RI outside of the context of disease progression. Overall response rate (52% vs 56%; P = .61) and survival outcomes (median progression-free survival, 4.6 vs 6.5 months; P = .62) were comparable in patients with and without RI, respectively, after a median follow-up of 9.9 months. No differences in overall survival or non-relapse mortality were noted. Our findings suggest that treatment with teclistamab is feasible in patients with RI, including those on dialysis, with a similar safety and efficacy profile to patients without RI.
由于临床试验将肾功能损害（RI）患者排除在外，双特异性抗体在这类患者中的疗效尚未得到充分描述。在此，我们评估了接受标准治疗药物替西妥单抗治疗的复发/难治性多发性骨髓瘤合并RI患者。RI定义为肌酐清除率（CrCl）<40 mL/分钟。CrCl<30 mL/分钟或依赖透析定义为严重RI。在纳入的384例患者中，81例（21%）有RI，其中45例（18%）为严重RI，18例（5%）接受透析。RI患者更可能年龄较大（中位年龄，71岁对67岁；P = 0.002），且既往治疗线数的中位数较高（7对6；P = 0.04）。有RI和无RI的患者中，细胞因子释放综合征的发生率和严重程度（51%对59%；≥3级：1.2%对1%）以及免疫效应细胞相关神经毒性综合征的发生率和严重程度（16%对13%；≥3级：2.5%对2.6%）分别相似。RI患者在基线时以及替西妥单抗治疗后第30天≥3级贫血和≥3级血小板减少症的发生率更高。在大多数疾病未进展的RI患者中，开始使用替西妥单抗后肾功能并未恶化。中位随访9.9个月后，有RI和无RI的患者总体缓解率（52%对56%；P = 0.61）和生存结果（中位无进展生存期，4.6个月对6.5个月；P = 0.62）分别相当。总生存期或非复发死亡率无差异。我们的研究结果表明，替西妥单抗治疗RI患者，包括透析患者是可行的，其安全性和疗效与无RI的患者相似。
